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According to the provisions of the Basic Law of our state, life and health, honor and dignity, inviolability and security of a person are the highest social value. In order to ensure the guaranteed right to health care, the state, in the form of authorized bodies, takes the necessary organizational and legal measures and methods aimed at preserving human health. The human right to health covers a wide range of health-related phenomena and practices. Standardization, licensing and accreditation as means of ensuring the human right to health care directly belong to this spectrum of social relations. Taking into account the fact that the health care of citizens is based on a number of principles enshrined in the Constitution and laws of Ukraine, the article emphasizes that standardization, licensing and accreditation, which are the guarantee of life and health care, occupy a specific weight in health care citizens. Through the prism of legislative regulation and the analysis of subordinate regulatory legal acts, the author of the article examines the impact of regulatory legal acts on the regulation of relations in the field of standardization, licensing, and accreditation. The author focuses on the activities of the Cabinet of Ministers of Ukraine, the Ministry of Health of Ukraine, the State Service of Ukraine for Medicinal Products and Drug Control, as well as other public administration entities that play a leading role in licensing, standardization and accreditation of business entities, as well as other participants in relations in the field of health care. In general, the article draws attention to the important role of public law entities in regulating relations in the field of standardization, licensing, and accreditation, as well as draws attention to the legal mechanism of compulsory licensing. It is concluded that the modern system of public administration in the researched sphere of public relations is carried out primarily by authorized state bodies. It is emphasized that the subject of further research should be the issue of determining the system of public and private law entities involved in the process of regulating relations in the sphere of health care of Ukraine, the disclosure of the legal mechanism of compulsory licensing in order to ensure the health of the population, the defense of the state, environmental safety and other public interests, as well as the activities of public entities during the martial law regime. [ABSTRACT FROM AUTHOR]

The article discusses the issues of polypharmacy and unjustified prescribing in pregnant women. The author— Honoured Scientist of the Russian Federation, Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Full Professor, and Head of the Department for Obstetrics and Gynaecology with a Course on Perinatology at the Institute of Medicine of the Peoples’ Friendship University of Russia named after Patrice Lumumba, Viktor E. Radzinskiy — questions the established practice of unnecessary hospitalisation of pregnant women without clinical indications and prescribing them numerous medicinal products, including antimicrobials, hormones, and antispasmodics. In most cases, pregnancy does not require medical intervention. The widespread use of progestogens in patients with threatened miscarriage lacks an evidence base. Antispasmodics, such as papaverine, are ineffective in threatened preterm labour. The author calls for a rational approach to prescribing medicinal products to pregnant women based on current clinical practice guidelines and the “do no harm” maxim. Viktor E. RADZINSKIY emphasises the need to follow clinical protocols and ensure physicians are informed about the evidence for the use of medicinal products in pregnancy to prevent polypharmacy and adverse consequences.

The off-label use of drugs is a common practice worldwide. The legal basis for off-label medical use varies from country to country. Regulatory control of the pharmaceutical market in the off-label preventive and therapeutic practice at the international and national levels has become a breakthrough with the emergence of the coronavirus pandemic. The prospects for off-label use in the context of innovations in the legislation of public health in the Russian Federation are crucial. Professionally significant aspects of the use of medicinal products outside the Summary of Product Characteristics and the off-label use have been introduced by supranational regulatory authorities for the common market of medicinal products of the Eurasian Economic Union. Special attention should be paid to the regulatory control of the use of extemporaneous medicines as part of improving the government regulation of drug compounding in pharmacies. The active development of pharmacy activities in drug compounding within the framework of improving regulatory practice determines the relevance of actual off-label prescriptions and the use of extemporaneous formulations. Aim – to perform a systematic analysis of national, transnational legislative and regulatory documents regulating off-label use of medicinal products, determine the main conceptual components of the current regulatory pool and directions for future development in this area. Systematic analysis of the national legislative and regulatory pool of documents and the regulatory framework of the common market of medicinal products of the Eurasian Economic Union on the regulation of various aspects of the off-label use of medicinal products. Study of the components and identification of the main trends in the regulatory practice of prescriptions outside the Summary of Product Characteristics and the off-label use. An analytical search was carried out in the reference legal systems "ConsultantPlus" and "Garant" on the official websites of the Ministry of Health of Russia, the Eurasian Economic Union, the RusMed information resource of the National Library resource of Russia in medicine and pharmacy "Central Scientific Medical Library" was used. A logical generalization of the results on the current state of the legal framework and the development of conceptual proposals on the key directions of the prospective development of regulation, control, and supervisory activities of the pharmaceutical off-label use of medicinal products was made.

Children deserve to be treated with appropriate medicines based on robust assessments. Despite the introduction of new regulations, the availability of medicines for children is suboptimal because of the frequent lack of relevant clinical trials due to the difficulty of conducting such trials. Thus, the Transparency Committee (TC) of the French National Authority for Health, who oversees the assessment of medicinal products in France, set up a pediatric working group with two aims: (1) The first aim was to review all opinions on medicines for pediatric use. Out of 536 opinions delivered between 2020 and 2022, 181 (34 %) concerned medicines for pediatric use. Whereas oncology largely dominated the medicines for adults, medicines for infectious diseases, endocrinology/metabolism, neurology, and hematology mostly prevailed for children. (2) The second aim was to clarify the evaluation criteria assessed by the TC, namely, the clinical benefit (CB), the clinical added value (CAV), and the public health impact (PHI) for pediatric medicinal products. An important CB was given to 113 out of 161 (71 %) opinions on medicines for pediatric use when it concerned pathologies with a severe prognosis. The quality of the demonstration (e.g., double-blind randomized trial vs. placebo or another active medicine) played a major role in the CB level. Clinical pediatric studies were also consistently associated with higher CAV levels: levels I (major) to III (moderate) in 26 out of 42 (62 %) opinions, level IV (minor) and level V (no therapeutic progress) in 43 out of 84 (51 %) and 30 out of 43 (70 %) opinions granting a sufficient CB, respectively. Conversely, 22 out of 30 (73 %) dossiers based only on literature reviews were given a level V. The main criteria leading to the qualification of a medicine for pediatric use as providing a PHI included a significant change in the morbidity and mortality of the disease and an improvement in the care pathway. Assessments were mostly aligned on the adults in the case of subsequent extensions of indications to children. Lastly, new measures were taken aimed at shortening median delays in the assessment process in order to reduce off-label use of medicines in France. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) hold great promise for clinical application as new diagnostic and therapeutic modalities. This paper describes major GMP-based upstream and downstream manufacturing processes for EV large-scale production, also focusing on post-processing technologies such as surface bioengineering and uploading studies to yield novel EV-based diagnostics and advanced therapy medicinal products. This paper also focuses on the quality, safety, and efficacy issues of the bioengineered EV drug candidates before first-in-human studies. Because clinical trials involving extracellular vesicles are on the global rise, this paper encompasses different clinical studies registered on clinical-trial register platforms, with varying levels of advancement, highlighting the growing interest in EV-related clinical programs. Navigating the regulatory affairs of EVs poses real challenges, and obtaining marketing authorization for EV-based medicines remains complex due to the lack of specific regulatory guidelines for such novel products. This paper discusses the state-of-the-art regulatory knowledge to date on EV-based diagnostics and medicinal products, highlighting further research and global regulatory needs for the safe and reliable implementation of bioengineered EVs as diagnostic and therapeutic tools in clinical settings. Post-marketing pharmacovigilance for EV-based medicinal products is also presented, mainly addressing such topics as risk assessment and risk management. [ABSTRACT FROM AUTHOR]

Many medicinal products are initially developed and tested in adults, and often, only a limited amount of data on their safety and efficacy in children exist. Consequently, paediatric healthcare providers sometimes need to make informed decisions about using medicinal products in children based on available fragmentary data. Ethical guidelines emphasise the importance of protecting children and ensuring they receive safe and effective medical treatments. Paediatric clinical trials should be conducted to provide evidence- based care with specific attention to minimise risks to children. This highlights the dilemma of finding a balance between protecting children and adolescents (and avoiding unnecessary clinical trials) and obtaining reliable, robust and justified data to treat them adequately and not in an off-label manner with unknown risks. For years, paediatricians maintained that children and adolescents are not treated based on up-to-date scientific knowledge and justification. The slogan "children are not small adults" summarised the concerns in a catch phrase. Different stakeholders have taken a variety of actions to address this concern. [ABSTRACT FROM AUTHOR]

INTRODUCTION. The determination of impurities is a key requirement for the quality assessment of medicines because impurities can significantly impact the quality and therapeutic effectiveness. Pharmacopoeias are the most important scientific and methodological guidelines for manufacturers developing medicinal product specifications and regulators assessing these specifications as part of registration dossiers. Therefore, it is essential to harmonise national and international approaches to impurities.AIM. This study aimed to analyse and summarise pharmacopoeial requirements for and methodological approaches to the control, evaluation, and identification of organic impurities in medicines.DISCUSSION. The authors compared requirements for the control of organic impurities in small-molecule medicines set forth in national and international pharmacopoeias and guidelines of the International Council for Harmonisation of Technical Requirements for Medicinal Products for Medical Use (ICH) and the Eurasian Economic Union (EAEU). This comparison highlighted the differences in current approaches that require further harmonisation of the existing regulatory documentation. Additionally, this study analysed the popularity, advantages, and disadvantages of different options for determining impurities in two-component combination products (i.e. identified and/or unidentified impurities in one or each of the active substances). The analysis demonstrated the need to control nitrosamines and genotoxic impurities and to use selective and highly sensitive chromatographic methods.CONCLUSIONS. When drafting pharmacopoeial monographs for medicinal products, experts should consider the general approach set forth in the EAEU pharmacopoeia and regulations and in the ICH Q3B guideline. This approach recommends that process-related impurities of active substances should not be controlled at the medicinal product level. Therefore, pharmacopoeial monographs for active substances should distinguish degradation products from process-related impurities. Impurities should be determined for each active substance to ensure the quality and safety of fixed combination medicinal products. Priorities for improving the methodological approach to the control of organic impurities include using reference standards for impurities and acknowledging the necessity of impurity quantification.

The origins of the journal Safety and Risk of Pharmacotherapy date back to 1994. The journal was published as Safety of Medicinal Products, Safety of Medicines, and Safety of Medicinal Products and Pharmacovigilance. In Russia, this journal has always been the only specialised scientific publication covering exclusively the safety of pharmacotherapy. Alla V. Astakhova, Candidate of Medical Sciences, headed the journal from 1994 to 2015.The history of the journal is closely intertwined with the history of the pharmacovigilance system in Russia. Vladimir K. Lepakhin, Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences, has made an outstanding contribution to the development of the Russian pharmacovigilance system. This joint interview with Alla V. Astakhova and Vladimir K. Lepakhin presents the major milestones in the development of the journal and the Russian pharmacovigilance system.

SCIENTIFIC RELEVANCE. The pandemic of novel coronavirus infection (COVID-19) led to a drastic increase in the use of medicinal products of various therapeutic groups and increased spontaneous reporting of adverse drug reactions (ADRs). Therefore, it is necessary to analyse the reported information to identify potential safety signals.AIM. This study aimed at systematisation and quantitative analysis of data on the safety of COVID-19 medicinal products from the Russian pharmacovigilance database.MATERIALS AND METHODS. This retrospective analysis included spontaneous ADR reports submitted to the Russian pharmacovigilance database from 1 January 2020 to 31 December 2022. The authors applied disproportionality analysis to generate safety signals.RESULTS. During the stated period, the database website published 873 spontaneous reports on 1,636 ADRs associated with COVID-19 treatment. Most ADRs were associated with favipiravir (493 reports), hydroxychloroquine (87 reports), and olokizumab (85 reports). The most common ADRs included 273 (16.7%) abnormal investigation results, 203 (12.4%) hepatobiliary disorders, and 191 (11.6%) gastrointestinal disorders. The majority of adverse events, 674 (77%) cases, had favourable outcomes. Using frequency-based disproportionality analysis, the authors identified 23 potential safety signals based on disproportionately reported ADRs for azithromycin, dexamethasone, levilimab, lopinavir+ritonavir, molnupiravir, olokizumab, tofacitinib, tocilizumab, umifenovir, and favipiravir.CONCLUSIONS. The new safety signals require additional assessment of ADR reporting forms for causal relationship analysis, validation, prioritisation, and clinical interpretation. The frequency-based method did not identify safety signals for hydroxychloroquine, remdesivir, baricitinib, sarilumab, and anti-COVID-19 human immunoglobulin, but this does not rule out the possibility of detecting new causal relationships.

The article considers the problems of distinguishing criminal offenses trespassing pharmaceutical activity from related criminal offenses. The author claims that the separation of criminal offenses trespassing pharmaceutical activity from related criminal offenses is due to the need to provide an accurate, justified and complete criminal legal assessment of the committed encroachment. Finding out the features of the mechanism of distinguishing criminal offenses trespassing pharmaceutical activity from related criminal offenses, the author suggests taking into account the following main points: 1) characteristics of the victims (Articles 137, 140, 141, 142 of the Criminal Code); 2) signs of objects (Articles 141, 321-2 of the Criminal Code); 3) signs of actions and their consequences (Articles 131, 134, 137, 140 of the Criminal Code); 4) signs of actions, ways of committing them and their consequences (Part 2 of Article 308, Part 2 of Article 312, Part 2 of Article 313, Part 2 of Article 321-1 of the Criminal Code). Carrying out a systematic analysis of the provisions of the Criminal Code of Ukraine, the author cites specific situations with his own vision of how certain criminal offenses trespassing pharmaceutical activity should be distinguished from related criminal offenses. In particular, how should the elements of the criminal offense provided for in Art. 137 of the Criminal Code, where the victims are minors (children), in relation to whom subjects of medical and pharmaceutical services are obliged to take measures to ensure the protection of their life and health with a qualified staff of improper performance of professional duties by a medical or pharmaceutical worker, where a minor the person is also a victim. The article focuses attention on the contiguity of types of professional negligence in the field of medical and pharmaceutical activity (Articles 131, 137, 140 of the Criminal Code) and official negligence (Article 367 of the Criminal Code). The author comes to the conclusion that the concept of falsified medicinal products (Article 321-1 of the Criminal Code) can be associated with the forgery of documents (Articles 358, 366 of the Criminal Code) and the use of knowingly forged documents (Part 4 of Article 358 of the Criminal Code). [ABSTRACT FROM AUTHOR]

Dendrobium brymerianum Rchb. f. is a species of orchid with pharmacological interest for its potential to inhibit the growth of human lung cancer cells. The identification of the Dendrobium species is a notable problem due to morphological similarities and the limitations of universal DNA barcodes. To overcome these difficulties, this study employed complete chloroplast (cp) genome sequences as useful resources for the identification of D. brymerianum. Based on Illumina sequencing, the complete cp genomes of five D. brymerianum individuals were assembled. These genomes were in the quadripartite structure, diverse in length between 151,832 and 152,189 bp, and comprised 126 genes. Moreover, significant differences were found in the Small Single-Copy (SSC) and Large Single-Copy (LSC) regions in comparison to the Inverted Repeat (IR) regions. This study recognized hotspot regions and simple sequence repeat (SSR) loci, providing valuable insights into genetic markers. The phylogenetic relationship of Dendrobium species was discovered, highlighting the need for more precise differentiation practices. To address this, ARMS-specific primers, mainly AAob1/AAob2, confirmed strong specificity, permitting the accurate identification of D. brymerianum from other species through ARMS-qPCR. Overall, this study of D. brymerianum chloroplast genomes has generated valuable data about sequence variations, phylogenetics, and mutation dynamics. These perceptions will be valuable in future research on population genetics, taxonomy, and species identification within the Dendrobium genus. [ABSTRACT FROM AUTHOR]

Many medicinal products are initially developed and tested in adults, and often, only a limited amount of data on their safety and efficacy in children exist. Consequently, paediatric healthcare providers sometimes need to make informed decisions about using medicinal products in children based on available fragmentary data. Ethical guidelines emphasise the importance of protecting children and ensuring they receive safe and effective medical treatments. Paediatric clinical trials should be conducted to provide evidence-based care with specific attention to minimise risks to children. This highlights the dilemma of finding a balance between protecting children and adolescents (and avoiding unnecessary clinical trials) and obtaining reliable, robust and justified data to treat them adequately and not in an off-label manner with unknown risks. For years, paediatricians maintained that children and adolescents are not treated based on up-to-date scientific knowledge and justification. The slogan “children are not small adults” summarised the concerns in a catch phrase. Different stakeholders have taken a variety of actions to address this concern.

Scientific relevance. Obesity is a significant public health problem. Currently, the Russian Federation and the other Member States of the Eurasian Economic Union (EAEU) do not have regulatory documents and recommendations for planning clinical trials (CTs) of new (original) medicines for the treatment of obesity.Aim. The study aimed to provide recommendations on the basic principles of planning and conducting CTs of medicines for the treatment of obesity.Discussion. The authors reviewed the requirements for conducting CTs of medicines for the treatment of obesity set forth by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). In addition, the authors analysed approaches to CTs providing for a reliable evaluation of the efficacy and safety of medicines for the treatment of obesity. The primary endpoint of such CTs is a statistically significant loss of at least 5% of the baseline weight after 12 months of treatment. Secondary endpoints include assessments of abdominal obesity reduction, subcutaneous and visceral fat reduction, and the medicinal product’s effect on maintaining a reduced body weight.Conclusions. In addition, CTs should investigate the effects of treatment on cardiovascular risk factors and cardiovascular morbidity/mortality. A CT protocol should define the intercurrent events that should be considered in the analysis of trial results. When investigating the safety of medicines for the treatment of obesity, studies should focus on neuropsychiatric safety, the potential for abuse/addiction and withdrawal reactions, and the development of valvulopathy and pulmonary hypertension. These recommendations may be of use to experts evaluating clinical development programmes or marketing authorisation submissions for medicines for the treatment of obesity.

Scientific relevance. Since fiscal and regulatory constraints substantially limit bioscreening in rodent models, a wider implementation of additional alternative models in preclinical studies of medicines is gaining momentum. These alternative models include aquatic vertebrates, such as zebrafish (Danio rerio).Aim. The study aimed to examine zebrafish models in terms of their performance in preclinical studies, their current uses, the challenges and opportunities in the field, and strategic directions for the development of preclinical testing in zebrafish.Discussion. Here, the authors summarise the key zebrafish tests that are currently used to assess a wide range of small molecules for their general and endocrine toxicity and effects on the survival of embryos and larvae. The review discusses the strengths and weaknesses of zebrafish models for preclinical testing of neurotropic agents. Additionally, the authors overview various methodological approaches to improving zebrafish toxicity testing. Overall, the use of zebrafish models is gradually becoming internationally established for laboratory testing of small molecules.Conclusions. A wider implementation of zebrafish models in pharmaceutical research and preclinical testing as an additional alternative to rodents, particularly in Russia, may significantly accelerate the development of novel medicinal products and foster a more comprehensive and adequate assessment of the biological risks associated with chemical substances.

Scientific relevance. This article describes a risk-based analysis of the need for elaborating pharmacopoeial requirements for 6 therapeutic groups of medicines, including an evaluation of the range and number of batches of these medicines put into the stream of commerce in the Russian Federation and a comparison of the corresponding product specification files and quality standards. The article presents a set of criteria for planning the elaboration of monographs for the State Pharmacopoeia of the Russian Federation according to a risk-based approach, which is used in a variety of other fields.Aim. The study aimed to develop a comprehensive multivariate risk-based system providing criteria for planning the elaboration of monographs for the State Pharmacopoeia of the Russian Federation.Materials and methods. This study focused on medicines for human use under a range of international non-proprietary names. The authors analysed entries in the Russian State Register of Medicines, data on the number of batches released to the pharmaceutical market, and product specification files and quality standards. The study was conducted using literature search, data analysis, and system-oriented methods.Results. According to the results, a multivariate risk-based analysis is needed for planning the elaboration of monographs for the State Pharmacopoeia of the Russian Federation and the subsequent prioritisation of therapeutic groups or individual medicines for their standardisation.Conclusions. The suggested risk-based system for planning the elaboration of monographs for the State Pharmacopoeia of the Russian Federation includes the following criteria: the social significance of a medicinal product and its value for the health care system; the percentage of medicinal products not tested by the national regulatory authority at the level of active pharmaceutical ingredients; the substantial number of batches and the significant range of medicinal products and the respective active pharmaceutical ingredients by different manufacturers present in the pharmaceutical market; and the analytical procedures and requirements established in product specification files and quality standards.

Background. As the global burden of neurological diseases has been increasing, clinical trials have become more important. Yet, no systematic analysis of clinical trials of neurological medicinal products has been done in Europe and, specifically, in Lithuania. The aim of this study is to evaluate the tendencies of characteristics and registration dynamics of clinical trials of neurological medicines in Europe and Lithuania.Materials and methods. Analysis of data from the clinical trials register of the European Union drug regulatory authorities (EudraCT) has been performed. Applications of clinical trials of neurological medicines included in the register during the period between 2012–2021 have been reviewed. The following aspects have been evaluated: the phase of the trial, the sponsor status, the neurological condition (indication), the expected sample size of the trial, the trial design, and the number of member countries.Results. 2,242 clinical trials of neurological medicines have been registered in Europe during the period of 2012–2021, and they comprised 6.49% of all clinical trials registered in Europe. The annual registration rates did not change significantly during the period of 2012–2021 (R² = 0.039; p = 0.606). The majority of the trials (72.18%) were sponsored by commercial pharmaceutical companies. Most trials (31.73%) were registered as phase I trials. The majority of the trials (363 (17.20%)) were clinical trials for Alzheimer’s disease and other dementias. During the period of 2012–2021, there was a significant decrease in the annual registration rate of clinical trials for Alzheimer’s disease and other dementias (R² = 0.751, p = 0.001) and an increase of clinical trials for myoneural junction and muscle diseases and motor neuron disease (R² = 0.582, p = 0.010 and R² = 0.635, p = 0.006, accordingly). Commercial trials had a higher planned number of subjects (p = 0.014). Multiple member states participated in commercial trials more frequently (p < 0.001). Fifty-five clinical trials of neurological medicines were registered in Lithuania during the period of 2012–2021, and they comprised 8.08% of all clinical trials registered in Lithuania. The annual registration rate has decreased significantly (R² = 0.401, p = 0.049). Almost all trials in Lithuania (53 out of 55) were sponsored by commercial companies. The majority of trials (23 (42%)) were trials for demyelinating diseases of the CNS.Conclusions. The annual registration rates of trials of neurological medicines remain stable in Europe while decreasing in Lithuania. Commercial clinical trials have more participants, and are more commonly conducted in multiple member states.

Pharmaceutical companies frequently engage in drug advertising to connect with potential buyers. In the competitive pharmaceutical market, where patients are highly sensitive to various forms of advertising, manufacturers aim to reach a broad audience. This rapid dissemination of information in the advertising of medicinal products leads to some details being unverified and inaccurate, which emphasizes the critical importance of establishing and enforcing legislation. This paper aims to evaluate the current legislation for advertising of medicinal products in Republic of North Macedonia, as well as the regulations in European Union member states, namely Germany, Slovenia and Spain. The basic legal act that regulates the advertising of medicinal products in the European Union is Directive 2001/83/EC of the European Parliament and of the Council of Europe of 6 November 2001 on the Community code relating to medicinal products for human use such as amended by Directive 2004/27/EC of 31 March 2004. By reviewing relevant literature and conducting a comparative analysis of regulations in the Republic of North Macedonia and European Union, it can be concluded that the European Directive serves as a foundational framework. Each country has transposed the European Directive in domestic laws and regulatory guidelines with local adaptations and all Member States have therefore adopted further specific measures concerning the advertising of medicinal products. Depending on the member state, pharmaceutical promotion can be monitored and controlled by the government, by a national competent authority or not, this approach is called “self-regulation.Upon examining the regulatory structures in each specific country, there are five key components that must be implemented: development and adoption of national laws and regulations; implementation of the regulation, codes and other standards; monitoring the pharmaceutical promotion to ensure compliance with legal regulations; enforcement of the law through suitable sanctions to prevent violations; and evaluation of regulatory efficiency. Drawing parallels between the practices of established European member states and the regulatory framework of the Republic of North Macedonia, it becomes evident that there is an opportunity for the Republic of North Macedonia to leverage positive experiences from the European countries. By incorporating successful elements of European member states' regulations, the Republic of North Macedonia could enhance its own pharmaceutical regulatory environment. Based on this evaluation of established practices and experiences in European countries, direction will be provided for harmonizing and improving the regulatory framework for advertising od medicinal products in the Republic of North Macedonia. [ABSTRACT FROM AUTHOR]

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The presented article provides a systematic review of the pharmaceutical legislation (EU Pharmaceutical Package) - the current proposal of the European Commission for a new Directive, repealing and replacing Directives and modifying Regulations of the European Parliament and of the Council, incorporating the relevant parts of the Regulation concerning medicinal products for pediatrics, Regulation for orphan drugs and others, aiming at revision of the pharmaceutical legislation in the context of antimicrobial resistance and challenges facing the introduction of innovative antimicrobial medicines in Europe. It outlines a critical analysis on the impact of the changes in the context of introduction of innovative antimicrobial medicinal products with an emphasis on unsatisfied medical demands of the European population. The revision of the pharmaceutical legislation provides an argument to consider that the proposed Pharmaceutical Package could resolve some of the issues associated with the access to novel antibiotic medicines. It is necessary to find a consensus and a balance between, on the one hand, meeting the need for antibiotics for the citizens of the European Union and, on the other hand, providing timely access to generic medicines to meet the needs of the population. [ABSTRACT FROM AUTHOR]

The article presents the results of a comparative analysis of regulatory requirements for expertise of clinical trials documentation, submitted for regulatory authority and ethic committees' approval in EU member countries and Ukraine, outlining the main trends, considering the updated Regulation (EU) No 536/2014, which came into effect on January 31, 2023. Among the positive changes are simplification of safety reporting requirements, use of artificial intelligence in the process of clinical trials documentation examination for obtaining regulatory authority and ethic commission approval, introduction of a single portal for submitting materials for clinical trials, and functioning of database for the submission and review of initial Clinical Trial Application documents and obtaining authorization within the EU to facilitate the interaction between applicants and regulatory authority are highlighted. To harmonize Ukraine's regulatory requirements with EU legislation, it is advisable to use a single portal for data exchange and document submission for applicants in regards to clinical trials, regulatory authority and local ethics committees. This will expedite the examination process of clinical trial documentation and simplify the monitoring of document review progress. [ABSTRACT FROM AUTHOR]

In the USA and the EU, there is a respected and strict regulatory approval process conducted by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), respectively. These regulatory agencies set guidelines for fundamental research and tests. Despite harmonized regulatory procedures, the approval processes for new drugs in the USA and the EU have their specific characteristics. The approval process for medicinal products in each country involves balancing conflicting social goals. Excessive scrutiny and analysis of a new drug inevitably slow down patient access to it and are likely to increase its cost, but it largely ensures its safety. The FDA often applies procedures for the priority status of new medicinal products, which shorten the regulatory approval timeframe compared to the EMA. This establishes the FDA as an undisputed leader in the review, evaluation, and approval of new medicinal products worldwide. [ABSTRACT FROM AUTHOR]

The article is devoted to the issue of causing harm to pharmaceutical activity as an object of criminal law protection. As the author notes, the current legislation regulating the procedure for pharmaceutical activity contains certain guidelines for determining harm to the specified social values or its individual fragments. In the opinion of the author, characterizing the formation of harm "within" pharmaceutical activity as an object of criminal law protection and its consideration in the composition of criminal offenses, it is necessary to determine the types of actions that affect pharmaceutical activity and lead to its violation - formation in it or in certain types of damage to its individual "components". The author consistently proves that the aspects of influence on pharmaceutical activity, which give the committed act the properties of public danger, should be associated with various indicators of damage caused to pharmaceutical activity as an independent object of criminal law protection. [ABSTRACT FROM AUTHOR]

Currently the medicinal products are authorized at European Union level by the European Commission or at national level by the competent authorities of the Member States. For medicinal products paid with public funds, their effectiveness is also subject to monitoring. Bulgaria ranks first in terms of mortality and last in terms of life expectancy in the EU. The average life expectancy for the country's population remains the lowest in the European Union, being as much as 7 years lower than the EU average. In this critical situation in Bulgaria, although in absolute terms the costs per capita are more than 25% lower than the corresponding costs in the European Union as a whole, medicines account for the largest share of costs among the EU countries — 36 .1%, which is twice than the average for the entire EU. Despite the observed trend of continuous growth of public expenditure in our country, the expenditure for medicinal products constitutes the predominant part of the expenditure for direct payments by patients [ABSTRACT FROM AUTHOR]

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Researchers need to identify the nephrotoxic properties of medicinal products both during preclinical development and when exploring options to optimise pharmacotherapy. The main challenge is to find an experimental model for assessing drug-induced nephrotoxicity that reflects in vivo conditions as closely as possible.The aim of the study was to compare the susceptibility of HEK293 and RPTEC cell lines used as experimental models for assessing the nephrotoxicity of cefuroxime and cefepime.Materials and methods. The study investigated HEK293 and RPTEC cell lines cultured on plates with 0.4 µm pore membrane inserts. The cell lines were incubated for 3 days with cefuroxime and cefepime (cephalosporins excreted primarily by the kidneys). The medicinal products were added to the basal part of the well at concentrations of 50 and 150 µg/mL (cefuroxime) or 30 and 120 µg/mL (cefepime) twice a day. After incubating the cells with cefuroxime and cefepime for 24, 48, and 72 hours, the authors determined the expression levels of the SLC22A6 and SLC22A8 genes encoding organic anion transporters by a reverse transcription polymerase chain reaction. The authors considered caspase 3 and caspase 7 activation indicative of the nephrotoxic effect of cephalosporins; they evaluated this indicator by a fluorometric assay after 24, 48, and 72 hours of incubation.Results. According to the study, the expression of the SLC22A6 and SLC22A8 genes decreased with cephalosporin transport in both cell lines. The decrease occurred in the RPTEC cell line earlier than in the HEK293 cell line. The authors observed caspase 3 and caspase 7 activation only in the RPTEC cell line after incubation with cefuroxime and cefepime at low concentrations (50 and 30 µg/mL, respectively) for 72 hours and at high concentrations (150 and 120 µg/mL, respectively) for 24 hours.Conclusions. The RPTEC cell line exhibits higher susceptibility to cefuroxime and cefepime toxic effects than the HEK293 cell line due to higher transporter gene expression. Higher cephalosporin concentrations accelerate caspase 3 and caspase 7 activation in the RPTEC cell line. The experimental model based on the RPTEC cell line is a promising tool for the analysis of the nephrotoxic properties of a wide range of medicinal products.

Medicinal products are a special type of goods due to their importance for human health and life, and their trade is generally under the scope of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. The preamble to this act states that the essential aim of the rules governing the production, distribution and use of medicinal products must be to safeguard public health. Hence, in the above-mentioned directive, the rules related to the authorisation of medicinal products for marketing and pharmacovigilance are very important. At the same time, it should be noted that parallel import of medicinal products as a form of trade in an EU Member State in connection with their authorisation for marketing in another Member State, although it has a long tradition, has not had a clear normative pattern, and has not been subject to the scope of Directive 2001/83/EC. It is based on the achievements of the acquis communautaire developed in this area and the principle of free movement of goods (Article 34 TFEU) and its exceptions set out in Article 36 TFEU concerning the protection of human health and life. The commented judgment sets an example of one more verdict confirming the interpretation of Articles 34 and 36 TFEU, according to which national provisions of a Member State should be considered unacceptable, according to which the withdrawal of the marketing authorisation for the reference medicinal product in the country of import has the automatic effect of expiring the parallel import authorisation. At the same time, new circumstances affecting the safety of the medicinal product on the market were analysed to give the conclusion as declared in the sentence.

Medicinal products are a special type of goods due to their importance for human health and life, and their trade is generally under the scope of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. The preamble to this act states that the essential aim of the rules governing the production, distribution and use of medicinal products must be to safeguard public health. Hence, in the above-mentioned directive, the rules related to the authorisation of medicinal products for marketing and pharmacovigilance are very important. At the same time, it should be noted that parallel import of medicinal products as a form of trade in an EU Member State in connection with their authorisation for marketing in another Member State, although it has a long tradition, has not had a clear normative pattern, and has not been subject to the scope of Directive 2001/83/EC. It is based on the achievements of the acquis communautaire developed in this area and the principle of free movement of goods (Article 34 TFEU) and its exceptions set out in Article 36 TFEU concerning the protection of human health and life. The commented judgment sets an example of one more verdict confirming the interpretation of Articles 34 and 36 TFEU, according to which national provisions of a Member State should be considered unacceptable, according to which the withdrawal of the marketing authorisation for the reference medicinal product in the country of import has the automatic effect of expiring the parallel import authorisation. At the same time, new circumstances affecting the safety of the medicinal product on the market were analysed to give the conclusion as declared in the sentence. [ABSTRACT FROM AUTHOR]

Purpose. Conducting an analysis of modern pharmaceutical production technologies and substantiating practical measures regarding the use of energy-efficient technologies in order to optimize and minimize energy consumption while preserving and guaranteeing the quality of finished products. Methodology. Analytical review of scientific, scientific-practical and statistical-analytical literature for the purpose of systematization and optimization of data that can be used for energy saving at enterprises of the pharmaceutical industry. Findings. The structure of energy consumption of the pharmaceutical industry was studied and ways of optimizing the energy efficiency of drug production were analyzed, which can be implemented both at the levels of individual stages, operations, processes, systems, and for the enterprise as a whole. A systematic analysis of production technologies and technological processes was carried out, ways of their optimization were proposed to minimize energy consumption and increase energy efficiency while maintaining the quality of finished products and increasing their competitiveness on the market. Originality. The theoretical aspects of energy-saving measures of pharmaceutical production are substantiated, ways of optimization and improvement of their energy efficiency, intensification of production processes, optimization of design and control of production processes and technological systems to achieve the cumulative effect of saving energy resources are proposed. Practical value. Determining measures to increase the energy efficiency of pharmaceutical production will allow to reduce energy consumption during production, to introduce measures for constant monitoring and control of consumed energy in order to ensure uninterrupted production processes and avoid reduction in the volume of production of medicines due to interruptions in energy supply. [ABSTRACT FROM AUTHOR]

The relevance of the conducted research is related to current challenges regarding the supply of medicines and their cost against the background of huge losses in the dead and wounded among the military and the civilian population, a decrease in the income of the population and an extremely difficult situation with a deficit of the state budget in Ukraine. Intellectual property rights, by limiting competition in the market, contribute to maintaining high prices for medicinal products and limiting sources of supply. At the same time, in the absence of patent barriers to market access for cheaper generic versions of medicines, optimal pricing and supply opportunities can be achieved. The purpose of this article is to study the ways of limiting intellectual property rights allowed by international law within the framework of the WTO TRIPS Agreement, which are the most convenient and effective in the conditions of a full-scale war, which will potentially contribute to the formulation of separate proposals for improving the legislation of Ukraine on relevant issues. Within the scope of the article, the authors describe the main ways and approaches available within the framework of international intellectual property law to limit intellectual property rights, the so-called TRIPS flexibilities, in order to ensure optimal access of the population to medical products and create an optimal balance between private rights and public interests. It was determined that the most effective and convenient for implementation in wartime would be the application of the security exception under Article 73 of the TRIPS Agreement. An analysis of the available legal practice on the application by other countries of the security exception in the framework of dispute settlement by the WTO Dispute Settlement Body was carried out. According to the two cases considered, the test for justifying the legitimacy of the application of the security exception by the WTO member countries, which was applied by the Dispute Settlement Body, was described and the potential compliance of the current situation in Ukraine with the requirements of the test was analyzed. In the conclusions based on the results of the conducted research, the directions for further improvement of the legislation of Ukraine in the field of intellectual property, taking into account the requirements of the WTO TRIPS Agreement, are suggested by the authors. [ABSTRACT FROM AUTHOR]

Zur Beurteilung der Wirksamkeit und Sicherheit eines neuen Wirkstoffes ist für die europäische Zulassungsbehörde (European Medicines Agency, EMA) die randomisierte kontrollierte Studie (RCT) der Goldstandard. Mit der Einführung des AMNOG (Arzneimittelmarktneuordnungsgesetz) am 01.01.2011 rückten methodische Aspekte zur geeigneten Beantwortung der relevanten Fragestellung, nämlich der Nutzenbewertung innovativer Pharmakotherapien gemäß § 35a SGB V, in den Vordergrund. Im Grundsatz wird für die Evaluation der relativen Wirksamkeit eines neuen Arzneimittels gegenüber der zweckmäßigen Vergleichstherapie (zVT) klinische Evidenz aus RCT als Bewertungsgrundlage herangezogen. Für Arzneimittel zur Therapie seltener Erkrankungen (Orphan Drugs, OD) bringt die Evidenzgenerierung mittels RCT besondere Herausforderungen mit sich. Aufgrund dessen traten für Orphan Drugs im Jahr 2000 die EU-gemeinschaftsrechtlichen Besonderheiten in Kraft mit dem Ziel, die Erforschung, Entwicklung und das Inverkehrbringen geeigneter Arzneimittel durch die pharmazeutische Industrie zu fördern (Verordnung (EG) Nr. 141/2000). Vor demselben Hintergrund gelten auch im AMNOG-Verfahren für Orphan Drugs besondere Regelungen, die die Ziele der europäischen Verordnung auf nationaler Ebene implementieren (§ 35a Abs. 1 S. 11 f. SGB V.). So gilt der Zusatznutzen von Orphan Drugs mit der Zulassung als belegt. Am 23.12.2021 veröffentlichte das Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) das Arbeitspapier GA21-01, im Rahmen dessen es sich kritisch mit dem Evidenzkörper und der Nutzenbewertung von Orphan Drugs auseinandersetzt (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) 2021). In dem Arbeitspapier nimmt das IQWiG einen Vergleich vor zwischen einer Nutzenbewertung der Orphan Drugs, die die Besonderheiten bei Markteintritt berücksichtigt (im Folgenden OD-Nutzenbewertung), und einer regulären Nutzenbewertung. Das IQWiG schlussfolgert aus seiner Analyse im Arbeitspapier GA21-01, dass auch für Orphan Drugs ausschließlich randomisiert kontrollierte Studien mit Vergleich gegenüber der zweckmäßigen Vergleichstherapie als Evidenzbasis für die Bewertung des Zusatznutzens berücksichtigt werden sollten.

The issue of occupational diseases in chemical and pharmaceutical workers is urgent because it stems from the rapid pace of development, the functional features, and the high biological activity of raw materials used by that industry. The study is aimed at summarizing the information on preconditions and nature of occupational diseases among chemical and pharmaceutical workers based on the analysis of literature data. An important prerequisite for the emergence of occupational diseases is the shortcomings in the production process, leading to pollution of surfaces and workspace air with chemicals through the use of semi-automatic equipment in particular. The harmful substances then enter the bodies of workers through the respiratory system, which is the main and most harmful way. The most dangerous processes are the production and processing of substances with high pharmacological activity, and thus the active pharmaceutical ingredients maybe considered to be the leading causative agents of occupational diseases in the industrial production of medicinal products. The range of diseases diagnosed in pharmaceutical workers is diverse and includes acute intoxication, effects on internal organs, reproductive function, changes in hormonal status, and changes in the hemic system and nervous system. The most common are diseases of respiratory organs and diseases of allergic origin. As a result, influential international organizations and many authors emphasize the need to develop criteria and methods for assessing the harmful effects of medicinal products on the health of workers when authorizing their production.

Serious adverse drug reactions (ADRs) to medicinal products can cause death. It is an immediate challenge for modern medicine to prevent the possibility of this outcome and to improve the safety of pharmacotherapy. The aim of this study was to identify and analyse the main methodological approaches to studying the prevalence, patterns, and risk factors of fatal ADRs. The authors identified three main methods for studying such reactions: analysis of death certificates, monitoring of spontaneous reports, and review of clinical trials with a particular focus on safety. Each of these methods has its advantages and limitations. Clinical trials provide the most accurate information on the prevalence of fatal ADRs. For inpatients, this value ranged from 0.05 to 0.95% of the total number of hospital admissions. Data from death certificates may be particularly useful for identifying the groups of medicinal products posing a high risk of death and for making longitudinal comparisons. Monitoring of spontaneous reports is very effective in rapidly identifying fatal adverse reactions to new medicinal products. According to the authors, not only the choice of a data collection method, but also its application can affect the results of an ADR study. It was noted that the data varied across clinical trials conducted in different countries. Such variations indicate the importance of studying the problem of fatal ADRs at the national level, as well as the need for initiating such studies in the Russian Federation.

Background. As the global burden of neurological diseases has been increasing, clinical trials have become more important. Yet, no systematic analysis of clinical trials of neurological medicinal products has been done in Europe and, specifically, in Lithuania. The aim of this study is to evaluate the tendencies of characteristics and registration dynamics of clinical trials of neurological medicines in Europe and Lithuania. Materials and methods. Analysis of data from the clinical trials register of the European Union drug regulatory authorities (EudraCT) has been performed. Applications of clinical trials of neurological medicines included in the register during the period between 2012–2021 have been reviewed. The following aspects have been evaluated: the phase of the trial, the sponsor status, the neurological condition (indication), the expected sample size of the trial, the trial design, and the number of member countries. Results. 2,242 clinical trials of neurological medicines have been registered in Europe during the period of 2012–2021, and they comprised 6.49% of all clinical trials registered in Europe. The annual registration rates did not change significantly during the period of 2012–2021 (R² = 0.039; p = 0.606). The majority of the trials (72.18%) were sponsored by commercial pharmaceutical companies. Most trials (31.73%) were registered as phase I trials. The majority of the trials (363 (17.20%)) were clinical trials for Alzheimer’s disease and other dementias. During the period of 2012–2021, there was a significant decrease in the annual registration rate of clinical trials for Alzheimer’s disease and other dementias (R² = 0.751, p = 0.001) and an increase of clinical trials for myoneural junction and muscle diseases and motor neuron disease (R² = 0.582, p = 0.010 and R² = 0.635, p = 0.006, accordingly). Commercial trials had a higher planned number of subjects (p = 0.014). Multiple member states participated in commercial trials more frequently (p < 0.001). Fifty-five clinical trials of neurological medicines were registered in Lithuania during the period of 2012–2021, and they comprised 8.08% of all clinical trials registered in Lithuania. The annual registration rate has decreased significantly (R² = 0.401, p = 0.049). Almost all trials in Lithuania (53 out of 55) were sponsored by commercial companies. The majority of trials (23 (42%)) were trials for demyelinating diseases of the CNS. Conclusions. The annual registration rates of trials of neurological medicines remain stable in Europe while decreasing in Lithuania. Commercial clinical trials have more participants, and are more commonly conducted in multiple member states. [ABSTRACT FROM AUTHOR]

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The advertising of medicines and therapeutic pharmaceutical products is unique. It differs from advertisements promoting other goods, products and services. However, advertising remains one of the means of promoting drug products and informing consumers of their existence, in the same way as the products used in their manufacture. Pharmaceutical companies rely on advertising to market their drug products, so that pharmacists, doctors and consumers in general are aware of them. In Morocco, the history of the fight against disease is marked by the use of advertising to promote the eradication of epidemics and raise awareness of the need for vaccination to combat fatal diseases, more specifically malaria, rhinitis, plague, tuberculosis and trachoma, after Morocco suffered waves of epidemics that were repelled and treated with medicines, pharmaceutical products and vaccines. [ABSTRACT FROM AUTHOR]

Dendrobium brymerianum Rchb. f. is a species of orchid with pharmacological interest for its potential to inhibit the growth of human lung cancer cells. The identification of the Dendrobium species is a notable problem due to morphological similarities and the limitations of universal DNA barcodes. To overcome these difficulties, this study employed complete chloroplast (cp) genome sequences as useful resources for the identification of D. brymerianum. Based on Illumina sequencing, the complete cp genomes of five D. brymerianum individuals were assembled. These genomes were in the quadripartite structure, diverse in length between 151,832 and 152,189 bp, and comprised 126 genes. Moreover, significant differences were found in the Small Single-Copy (SSC) and Large Single-Copy (LSC) regions in comparison to the Inverted Repeat (IR) regions. This study recognized hotspot regions and simple sequence repeat (SSR) loci, providing valuable insights into genetic markers. The phylogenetic relationship of Dendrobium species was discovered, highlighting the need for more precise differentiation practices. To address this, ARMS-specific primers, mainly AAob1/AAob2, confirmed strong specificity, permitting the accurate identification of D. brymerianum from other species through ARMS-qPCR. Overall, this study of D. brymerianum chloroplast genomes has generated valuable data about sequence variations, phylogenetics, and mutation dynamics. These perceptions will be valuable in future research on population genetics, taxonomy, and species identification within the Dendrobium genus.

Interventions in the human germline, whether for purposes of therapy for a hereditary disease or for purposes of enhancement, are controversial. While enhancement is almost unanimously rejected, therapy-oriented intervention is not a priori regarded as unacceptable. The legal discussion so far has focused primarily on the questions of whether manipulation of the embryo's germline is permissible or whether the genetic manipulation of germ cells and the use of these germ cells for embryo generation is permissible. Up to now, the upstream questions regarding the systematic germline therapy development in clinical trials have been ignored, including questions as to whether the development of germline therapy would be legally permissible within the European Union framework of clinical studies. This article highlights the legal issues connected with the clinical development of germline intervention, provides an overview of the various answers to these legal questions, and indicates where further research and discussion are needed. [ABSTRACT FROM AUTHOR]

The experts of the Scientific Centre for Expert Evaluation of Medicinal Products analysed administrative decisions of foreign regulatory authorities on the recalls of antibacterial and antiprotozoal medicinal products and/or the need for labelling updates due to changes in the safety profile. The analysis revealed 16 decisions containing information on the following medicines registered in Russia: ertapenem, сeftriaxone, cefazolin, аmoxicillin, сefoperazone+sulbactam, piperacillin+tazobactam, сlindamycin, teicoplanin, rifampin, co-trimoxazole, hydroxychloroquine.

The paper presents recommendations on describing analytical procedures for evaluation of medicinal products in terms of sterility and microbiological quality in accordance with the State Pharmacopoeia of the Russian Federation and the Pharmacopoeia of the EAEU. These quality attributes should be covered in Product specification files for any medicinal product. The paper describes specific considerations for preparation of the corresponding sections of the Russian or EAEU Product specification files. It is necessary to provide and justify quality requirements, refer to or describe the recommended analytical procedure and indicate differences, if any, from the standard one. Standardisation of the approach to microbiological quality control of medicinal products will allow analysts to accurately perform the tests, get reliable results and ensure the safety of medicinal products.

Drug development requires high-tech, simple, and sensitive methods. AlphaLISA method was announced as a universal method that would fit the listed criteria. However, research of other works on the pharmacokinetics of drugs related to this method showed a small number of pharmacokinetic studies in clinical trials. In this review, we focused on not only the positive aspects of the Alpha method, but also its disadvantages.

Genotoxic lesions are not only a cause of genetic pathologies and cancer, but also the most common and significant factor of the etiopathology of cardiovascular and neurodegenerative disorders, reproductive losses, infertility, and aging. This requires careful monitoring of the use of potential genotoxicants including medicinal products (MPs), which are a group of compounds intentionally and routinely used by humans. Genotoxicity assesment is highly essential in preclinical drug safety studies. The aim of the study was to analyse the current situation and reveal possible ways of addressing methodological and regulatory issues in genotoxicology to enable proper conduction of drug safety preclinical studies. The article summarises basic concepts of the modern genetic toxicology development and highlights the history of research aimed at identifying mutagenic, clastogenic, and aneugenic effects. The authors analyse regulatory aspects of genotoxicological studies of MPs and consider issues of improving the strategy for genotoxicity testing. The paper gives information about the genotoxicity tests approved for MPs, recommendations for interchangeability of tests in relation to particular study characteristics. The authors carried out a comparative analysis of the tests’ pros and cons with an emphasis that the study of each MP is a separate scientific task. They discuss interpretation of results and prediction of MP carcinogenic potential in genotoxicological studies. Recommendations are given for the optimisation of the MP genotoxicity assessment strategy, considering its partial integration into general toxicity studies. The article stresses the urgent need to develop registration methods for genotoxic events in germ cells, assesses the prospects of new tests, and reviews new trends in drug genotoxicology fundamental research.

Vaccines have continued to play a crucial global role in preventing infectious diseases in the twenty-first century. The Covid-19 pandemic has underlined their importance, with vaccines seen as the best way to protect the public from coronavirus. A longstanding problem of governments has been the extent to which they should assume responsibility for the compensation of those injured by vaccines. This paper reappraises the vaccine damage schemes currently available in the US and UK in the light of the Covid-19 pandemic. It argues that any improvements to both US and UK schemes should be included in a revised national vaccine policy which takes into consideration their respective long-term national vaccine strategies to prepare for future pandemics. It supports the adoption of a UK-wide National Vaccine Injury Compensation Programme, similar to the one in the US, to be administered by the Secretary of State for Health and Social Care. To balance the need for rigorous criteria to determine causation with the need for fairness, the programme should adopt the US practice of allowing negotiated settlements between parties in circumstances where review of the evidence has not concluded that the vaccine(s) caused the alleged injury but there are close calls concerning causation. [ABSTRACT FROM AUTHOR]

The quality of pharmaceuticals has always been a concern to the World Health Organization (WHO) from the beginning its inception. Good Manufacturing Practice (GMP) is an important part of a comprehensive system of quality assurance (QA) for both manufacturers and the government. In Lebanon, and since its application, many challenges faced the implementation of the QA program according to GMP guidelines. Yet, this program has been successfully implemented in the Lebanese pharmaceutical industry supported by the Lebanese Ministry of Public Health (MOPH), and the commitment of the national GMP committee, in addition to the involvement of the public and private pharmaceutical sectors. The main objective of this study is to evaluate the implementation of the QA program according to GMP guidelines by selected Lebanese pharmaceutical companies. A descriptive analytical study was conducted between August-November of 2018, using a questionnaire that was administered to the quality departments of 10 Lebanese pharmaceutical companies. Finding showed that all these companies were implementing the QA programs according to GMP guidelines (100%), where 60% of their quality managers are experienced in GMP guidelines for more than 6 years. Further, 50% of these companies were applying QA program according GMP guidelines since more than 6 years, and 80% of them are formulating their programs using all the quality tools of the international GMP standards. Moreover, 80% of them are establishing awareness toward the implementation of GMP guidelines through training by internal expertise and external consultants. On the other hand, the implementation cost was the most important challenge faced by 60% of these firms. Finally, all companies are profiting by an increase in efficacy and efficiency, better product quality, and decrease in defects due to the implementation of the GMP guidelines. All the Lebanese pharmaceutical companies are working toward developing their program to meet the international standards, yet, they still need governmental support to spread and compete around the world. [ABSTRACT FROM AUTHOR]

This article addresses the issue of advertising of medicinal products from the perspective of protecting the consumer’s interest. As the research problem of the article was chosen to reconstruct the normative pattern of indirect consumer protection against incompatible with the provisions of PrFarm advertising of medicinal products directed to the public. The paper uses the dogmatic-legal method. In order to be able to solve the research problem posed, it was necessary to analyze the current state of the law with reference to doctrine and case law. The chosen research method made it possible to answer the research questions posed in the study concerning, among other things, whether the current form of supervision of advertising of medicinal products (or more precisely: supervision of the legality of advertising of medicinal products) is sufficient, and whether the patient/consumer is effectively protected from inconsistent PrFarm advertising of medicinal products directed to the public. As a result of the study, it was concluded that the current regulations on supervision of advertising of medicinal products to the public are not sufficiently effective, as they do not sufficiently protect the interests of the consumer. The above made it possible to propose changes to the current regulations in the form of introducing ex ante control of advertising of medicinal products to the public.

The issue of occupational diseases in chemical and pharmaceutical workers is urgent because it stems from the rapid pace of development, the functional features, and the high biological activity of raw materials used by that industry. The study is aimed at summarizing the information on preconditions and nature of occupational diseases among chemical and pharmaceutical workers based on the analysis of literature data. An important prerequisite for the emergence of occupational diseases is the shortcomings in the production process, leading to pollution of surfaces and workspace air with chemicals through the use of semi-automatic equipment in particular. The harmful substances then enter the bodies of workers through the respiratory system, which is the main and most harmful way. The most dangerous processes are the production and processing of substances with high pharmacological activity, and thus the active pharmaceutical ingredients maybe considered to be the leading causative agents of occupational diseases in the industrial production of medicinal products. The range of diseases diagnosed in pharmaceutical workers is diverse and includes acute intoxication, effects on internal organs, reproductive function, changes in hormonal status, and changes in the hemic system and nervous system. The most common are diseases of respiratory organs and diseases of allergic origin. As a result, influential international organizations and many authors emphasize the need to develop criteria and methods for assessing the harmful effects of medicinal products on the health of workers when authorizing their production. [ABSTRACT FROM AUTHOR]