Pub Date : 2019-06-05DOI: 10.30895/1991-2919-2019-9-2-123-130
A. Ioutsi, M. Sumtsov, D. A. Artyushenko, D. Bychenkov, A. N. Blinov
The traditional gas-liquid chromatography (GLC) method using packed columns is still used in pharmaceutical analysis for determination of parabens, despite the fact that this technique has a number of serious drawbacks.The aim of the study was to develop a more effective capillary GLC method for determination of parabens in active pharmaceutical ingredients and finished pharmaceutical products.Materials and methods: the study was performed using Agilent 6890N and Agilent 7890B systems with flame-ionisation detectors. The systems were equipped with Agilent 7683B and Agilent G4513A autosamplers, respectively. The following columns were used in the study: ZB-1 15 m х 0.32 mm х 0.25 pm, DB-1 30 m х 0.32 mm х 3.0 pm, Cp-Sil 5-CB 30 m х 0.32 mm х 3.0 pm.Results: the authors developed a method for methylparaben and propylparaben determination using capillary column GLC. The chromatographic parameters (chromatographic system performance, reproducibility of peak areas, peak asymmetry) were determined for both capillary and packed column GLC. The authors outlined the prospects for simultaneous determination of several compounds using the proposed method: a four-component mixture containing methyl-, ethyl-, propyl-, and butylparaben was separated in 9 minutes. The authors used Loma Lux Psoriasis to perform partial validation of the test method. They determined the linearity range and the limit of quantitation for methylparaben and propylparaben, and verified accuracy and intermediate precision of the test method.Conclusions: the results of the study allowed for selection of optimal chromatographic conditions for rapid and high-precision determination of methylparaben and propylparaben in medicinal products. The developed method is recommended for control of the content of these compounds in medicinal products.
传统的填充柱气液色谱法(GLC)在药物分析中仍被用于对羟基苯甲酸酯的测定，尽管这种技术有许多严重的缺点。本研究的目的是建立一种更有效的毛细管气相色谱法测定药物活性成分和成品中对羟基苯甲酸酯的含量。材料和方法:本研究使用带有火焰电离检测器的Agilent 6890N和Agilent 7890B系统进行。系统分别配备Agilent 7683B和Agilent G4513A自动进样器。所用色谱柱为:ZB-1 15 m, 0.32 mm, 0.25 pm; DB-1 30 m, 0.32 mm, 3.0 pm; Cp-Sil - 5-CB, 30 m, 0.32 mm, 3.0 pm。结果:建立了毛细管色谱法测定对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的方法。测定了毛细管色谱和填充柱色谱的色谱参数(色谱系统性能、峰面积重现性、峰不对称性)。作者概述了使用该方法同时测定几种化合物的前景:在9分钟内分离出含有甲基，乙基，丙基和对羟基苯甲酸丁酯的四组分混合物。作者使用Loma Lux牛皮癣对测试方法进行部分验证。确定了对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的线性范围和定量限，验证了测试方法的准确度和中间精密度。结论:研究结果为快速、高精度测定药品中对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的色谱条件选择提供了依据。建议本方法用于药品中这些化合物的含量控制。
{"title":"Applicability of Capillary Gas-Liquid Chromatography for Determination of Parabens in Pharmaceutical Analysis","authors":"A. Ioutsi, M. Sumtsov, D. A. Artyushenko, D. Bychenkov, A. N. Blinov","doi":"10.30895/1991-2919-2019-9-2-123-130","DOIUrl":"https://doi.org/10.30895/1991-2919-2019-9-2-123-130","url":null,"abstract":"The traditional gas-liquid chromatography (GLC) method using packed columns is still used in pharmaceutical analysis for determination of parabens, despite the fact that this technique has a number of serious drawbacks.The aim of the study was to develop a more effective capillary GLC method for determination of parabens in active pharmaceutical ingredients and finished pharmaceutical products.Materials and methods: the study was performed using Agilent 6890N and Agilent 7890B systems with flame-ionisation detectors. The systems were equipped with Agilent 7683B and Agilent G4513A autosamplers, respectively. The following columns were used in the study: ZB-1 15 m х 0.32 mm х 0.25 pm, DB-1 30 m х 0.32 mm х 3.0 pm, Cp-Sil 5-CB 30 m х 0.32 mm х 3.0 pm.Results: the authors developed a method for methylparaben and propylparaben determination using capillary column GLC. The chromatographic parameters (chromatographic system performance, reproducibility of peak areas, peak asymmetry) were determined for both capillary and packed column GLC. The authors outlined the prospects for simultaneous determination of several compounds using the proposed method: a four-component mixture containing methyl-, ethyl-, propyl-, and butylparaben was separated in 9 minutes. The authors used Loma Lux Psoriasis to perform partial validation of the test method. They determined the linearity range and the limit of quantitation for methylparaben and propylparaben, and verified accuracy and intermediate precision of the test method.Conclusions: the results of the study allowed for selection of optimal chromatographic conditions for rapid and high-precision determination of methylparaben and propylparaben in medicinal products. The developed method is recommended for control of the content of these compounds in medicinal products.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86740001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-05DOI: 10.30895/1991-2919-2019-9-2-118-122
D. P. Andreev, A. V. Kozlovich, S. S. Andreev, I. G. Rakov
The production of scientific and technical products is one of the most promising areas in terms of implementation of automation systems. The information system «Document management of scientific and technical product deliveries» is a set of unique resources that provides each of the participants with the opportunity to operate a single database of electronic documents and data in accordance with their respective access rights. The aim of the study was to assess the experience of practical application of the automated information system «Document management of scientific and technical product deliveries» and its role in the optimisation of the organisation’s activities. The article discusses the main results of the information system application for data storage and data management enabling the marketing of scientific and technical products. The paper provides a general assessment of how the software product helps meet the requirements for monitoring the production timeframe, automate the drafting and approval of work-related and financial documentation. It describes the process of electronic document exchange using the capabilities of CALS/PLM technologies. The paper illustrates the need to use the automated document flow for production and marketing of samples of pathogenic microorganism strains, certified reference standards for commercial enterprises, non-periodical publications. It outlines the prospects for further optimisation of channels of communication with external customers, and electronic exchange of documents. The benefits from the use of this system help reduce the time spent by managers and employees on the compilation of packages of documents and on the preparation of applications — by automating routine manipulations in processing incoming information and documents received as annexes to applications and requests. This information system was analysed to illustrate the benefits of digital technologies.
{"title":"Experience of Practical Application of the Automated Information System «Document Management of Scientific and Technical Product Deliveries»","authors":"D. P. Andreev, A. V. Kozlovich, S. S. Andreev, I. G. Rakov","doi":"10.30895/1991-2919-2019-9-2-118-122","DOIUrl":"https://doi.org/10.30895/1991-2919-2019-9-2-118-122","url":null,"abstract":"The production of scientific and technical products is one of the most promising areas in terms of implementation of automation systems. The information system «Document management of scientific and technical product deliveries» is a set of unique resources that provides each of the participants with the opportunity to operate a single database of electronic documents and data in accordance with their respective access rights. The aim of the study was to assess the experience of practical application of the automated information system «Document management of scientific and technical product deliveries» and its role in the optimisation of the organisation’s activities. The article discusses the main results of the information system application for data storage and data management enabling the marketing of scientific and technical products. The paper provides a general assessment of how the software product helps meet the requirements for monitoring the production timeframe, automate the drafting and approval of work-related and financial documentation. It describes the process of electronic document exchange using the capabilities of CALS/PLM technologies. The paper illustrates the need to use the automated document flow for production and marketing of samples of pathogenic microorganism strains, certified reference standards for commercial enterprises, non-periodical publications. It outlines the prospects for further optimisation of channels of communication with external customers, and electronic exchange of documents. The benefits from the use of this system help reduce the time spent by managers and employees on the compilation of packages of documents and on the preparation of applications — by automating routine manipulations in processing incoming information and documents received as annexes to applications and requests. This information system was analysed to illustrate the benefits of digital technologies.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87160149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-05DOI: 10.30895/1991-2919-2019-9-2-108-117
L. I. Mit’kina, Anastasiya K. Ericheva
Labeling is an important source of information about a medicinal product. The completeness and accuracy of labeling ensures correct identification, as well as safe and efficacious use of the product. The aim of the present paper was to perform comparative analysis of requirements for the design of medicinal product packages currently applicable in the Russian Federation and in the Eurasian Economic Union (EEU) in order to facilitate the introduction of Russian medicinal products into the EEU market. The EEU requirements for medicinal product labeling are described in laws and regulations stipulating medicinal products circulation in the EEU. The Russian requirements are laid out in Federal Law No. 61-FZ «On medicines circulation» dated April 12, 2010, the State Pharmacopoeia of the Russian Federation, and the Guideline on Medicinal Products Evaluation of the FSBI «SCEEMP» of the Ministry of Health of Russia. It was demonstrated that labeling requirements described in the EEU and Russian regulations largely overlap, but there are also a number of differences that are mainly related to the information on the medicinal product composition and different interpretation of the term «herbal medicinal product». A successful promotion of Russian medicines in the EEU market will require harmonisation of definitions and requirements used in the Russian legislation with those stipulated in the EEU regulations.
{"title":"Current Requirements for Information Content and Graphic Design of a Medicinal Product Package","authors":"L. I. Mit’kina, Anastasiya K. Ericheva","doi":"10.30895/1991-2919-2019-9-2-108-117","DOIUrl":"https://doi.org/10.30895/1991-2919-2019-9-2-108-117","url":null,"abstract":"Labeling is an important source of information about a medicinal product. The completeness and accuracy of labeling ensures correct identification, as well as safe and efficacious use of the product. The aim of the present paper was to perform comparative analysis of requirements for the design of medicinal product packages currently applicable in the Russian Federation and in the Eurasian Economic Union (EEU) in order to facilitate the introduction of Russian medicinal products into the EEU market. The EEU requirements for medicinal product labeling are described in laws and regulations stipulating medicinal products circulation in the EEU. The Russian requirements are laid out in Federal Law No. 61-FZ «On medicines circulation» dated April 12, 2010, the State Pharmacopoeia of the Russian Federation, and the Guideline on Medicinal Products Evaluation of the FSBI «SCEEMP» of the Ministry of Health of Russia. It was demonstrated that labeling requirements described in the EEU and Russian regulations largely overlap, but there are also a number of differences that are mainly related to the information on the medicinal product composition and different interpretation of the term «herbal medicinal product». A successful promotion of Russian medicines in the EEU market will require harmonisation of definitions and requirements used in the Russian legislation with those stipulated in the EEU regulations.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84992458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-05DOI: 10.30895/1991-2919-2019-9-2-85-92
T. A. Batuashvili, L. V. Simutenko, P. V. Shadrin, N. P. Neugodova
The paper considers insulin’s specific action on the patient’s body, types of insulin preparations and insulin analogues which are used for the treatment of diabetes, as well as applicable requirements for these products. It was demonstrated that determination of biological activity is one of the key quality parameters of this type of medicines. The paper summarises the methods used for evaluation of insulin and its analogues, which are based both on the hormone’s general action on the body (in vivo: double crossing, euglycemic clamp, etc.), and on certain aspects of the hormone’s interaction with the body systems (in vitro: receptor-binding assay, phosphorylation, metabolic methods). Due to the appearance of insulin biosimilars on the pharmaceutical market, the article raises the issue that the «Biological potency» parameter tested in animals should be kept as part of the product specification. The analysis of the in vivo and in vitro methods of biological activity determination convincingly demonstrates that animal models can not be replaced with the modern analytical methods based on cell cultures. Consequently, animal models are still necessary, as they allow for an adequate assessment of the quality of insulins in terms of «Biological potency». Taking into account the global trend towards reduction of animal testing, the authors point out the need to develop modern methods, the results of which will be comparable to the results of in vivo determination of the biological activity.
{"title":"Modern Approaches to Determination of the Biological Activity of Insulin and its","authors":"T. A. Batuashvili, L. V. Simutenko, P. V. Shadrin, N. P. Neugodova","doi":"10.30895/1991-2919-2019-9-2-85-92","DOIUrl":"https://doi.org/10.30895/1991-2919-2019-9-2-85-92","url":null,"abstract":"The paper considers insulin’s specific action on the patient’s body, types of insulin preparations and insulin analogues which are used for the treatment of diabetes, as well as applicable requirements for these products. It was demonstrated that determination of biological activity is one of the key quality parameters of this type of medicines. The paper summarises the methods used for evaluation of insulin and its analogues, which are based both on the hormone’s general action on the body (in vivo: double crossing, euglycemic clamp, etc.), and on certain aspects of the hormone’s interaction with the body systems (in vitro: receptor-binding assay, phosphorylation, metabolic methods). Due to the appearance of insulin biosimilars on the pharmaceutical market, the article raises the issue that the «Biological potency» parameter tested in animals should be kept as part of the product specification. The analysis of the in vivo and in vitro methods of biological activity determination convincingly demonstrates that animal models can not be replaced with the modern analytical methods based on cell cultures. Consequently, animal models are still necessary, as they allow for an adequate assessment of the quality of insulins in terms of «Biological potency». Taking into account the global trend towards reduction of animal testing, the authors point out the need to develop modern methods, the results of which will be comparable to the results of in vivo determination of the biological activity.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87487403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-05DOI: 10.30895/1991-2919-2019-9-2-101-107
V. Arkhipov, E. Sokova, G. I. Gorodetskaya, O. A. Demidova, T. Aleksandrova
This article looks into interchangeability and therapeutic equivalence of innovator and generic anticonvulsants — the first-generation and new antiepileptic drugs (AEDs). The results of a number of clinical trials assessing therapeutic equivalence of generic AEDs support the opinion that these medicines could only be substituted provided an ultra-cautious approach is used, even if the case involves only one International Nonproprietary Name, including, but not limited to different dosage forms of one and the same product. The aim of the study was to analyse factors leading to incorrect assessment of therapeutic equivalence of new and generic anticonvulsant drugs, and to improve methodological approaches to conducting clinical trials of these products. The paper cites data from Russian and foreign sources which state that the substitution of AEDs in some patients in full remission may result in adverse reactions or relapse of seizures. The analysis of the experience of scientific, expert, and regulatory institutions made it possible to develop a course of actions to be used when substituting AEDs and conducting clinical trials that assess therapeutic equivalence of new and generic anticonvulsants. The proposed methodology will help minimise potential health risks brought about by various factors that result in incorrect assessment of AEDs therapeutic equivalence and interchangeability.
{"title":"New Anticonvulsants: Interchangeability Issues and the Use of Generic Anticonvulsants in Clinical Practice","authors":"V. Arkhipov, E. Sokova, G. I. Gorodetskaya, O. A. Demidova, T. Aleksandrova","doi":"10.30895/1991-2919-2019-9-2-101-107","DOIUrl":"https://doi.org/10.30895/1991-2919-2019-9-2-101-107","url":null,"abstract":"This article looks into interchangeability and therapeutic equivalence of innovator and generic anticonvulsants — the first-generation and new antiepileptic drugs (AEDs). The results of a number of clinical trials assessing therapeutic equivalence of generic AEDs support the opinion that these medicines could only be substituted provided an ultra-cautious approach is used, even if the case involves only one International Nonproprietary Name, including, but not limited to different dosage forms of one and the same product. The aim of the study was to analyse factors leading to incorrect assessment of therapeutic equivalence of new and generic anticonvulsant drugs, and to improve methodological approaches to conducting clinical trials of these products. The paper cites data from Russian and foreign sources which state that the substitution of AEDs in some patients in full remission may result in adverse reactions or relapse of seizures. The analysis of the experience of scientific, expert, and regulatory institutions made it possible to develop a course of actions to be used when substituting AEDs and conducting clinical trials that assess therapeutic equivalence of new and generic anticonvulsants. The proposed methodology will help minimise potential health risks brought about by various factors that result in incorrect assessment of AEDs therapeutic equivalence and interchangeability.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78833808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-03-25DOI: 10.30895/1991-2919-2019-9-1-41-48
V. Shevtsov, Yu. V. Olefir, V. A. Merkulov, V. Bondarev, I. Indikova, E. E. Evreinova, A. Rukavishnikov, L. M. Khantimirova, D. Gorenkov
The management of post-approval changes to registration dossiers for medicinal products is one of the most important factors for ensuring sustainable quality, safety and efficacy of medicines. Competent authorities that use the module format of the registration dossier, i.e. the regulatory authorities of the European Union, USA and other members of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), and the Eurasian Economic Union (EEU), issue guidelines on changes to registration dossiers for pharmaceuticals and biologicals (immunological products). Vaccines (finished dosage forms) and vaccine antigens (active ingredients) are a specific group of immunobiological products which have great prophylactic importance for healthcare, and which are associated with challenging development and specific methods of manufacturing and quality control. The procedure of introducing post-approval variations to dossiers for immunobiological medicinal products is poorly reflected in the current Russian and EEU regulations. The World Health Organization (WHO) established a procedure described in the «Guidelines on procedures and data requirements for changes to approved vaccines». The purpose of the present study was to compare current Russian and international legislation in terms of regulatory requirements for post-approval сhanges to dossiers for immunobiological products. The Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation is drafting Guideline on introducing post-approval changes into dossiers for immunobiological medicines. The draft includes a detailed review of various categories of changes based on their importance, and a list of conditions and required documents for specific groups of medicines. This article summarises scientific and methodological approaches to evaluation of changes introduced in registration dossiers for vaccines in order to further improve the regulatory framework of the Russian Federation and the EEU.
{"title":"Post-approval Variations to Dossiers for Vaccines: Analysis of Regulatory and Methodological Approaches Used in the Russian Federation and Abroad","authors":"V. Shevtsov, Yu. V. Olefir, V. A. Merkulov, V. Bondarev, I. Indikova, E. E. Evreinova, A. Rukavishnikov, L. M. Khantimirova, D. Gorenkov","doi":"10.30895/1991-2919-2019-9-1-41-48","DOIUrl":"https://doi.org/10.30895/1991-2919-2019-9-1-41-48","url":null,"abstract":"The management of post-approval changes to registration dossiers for medicinal products is one of the most important factors for ensuring sustainable quality, safety and efficacy of medicines. Competent authorities that use the module format of the registration dossier, i.e. the regulatory authorities of the European Union, USA and other members of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), and the Eurasian Economic Union (EEU), issue guidelines on changes to registration dossiers for pharmaceuticals and biologicals (immunological products). Vaccines (finished dosage forms) and vaccine antigens (active ingredients) are a specific group of immunobiological products which have great prophylactic importance for healthcare, and which are associated with challenging development and specific methods of manufacturing and quality control. The procedure of introducing post-approval variations to dossiers for immunobiological medicinal products is poorly reflected in the current Russian and EEU regulations. The World Health Organization (WHO) established a procedure described in the «Guidelines on procedures and data requirements for changes to approved vaccines». The purpose of the present study was to compare current Russian and international legislation in terms of regulatory requirements for post-approval сhanges to dossiers for immunobiological products. The Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation is drafting Guideline on introducing post-approval changes into dossiers for immunobiological medicines. The draft includes a detailed review of various categories of changes based on their importance, and a list of conditions and required documents for specific groups of medicines. This article summarises scientific and methodological approaches to evaluation of changes introduced in registration dossiers for vaccines in order to further improve the regulatory framework of the Russian Federation and the EEU.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"2011 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82576575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-03-25DOI: 10.30895/1991-2919-2019-9-1-6-13
A. Gubenko, N. Eremenko
In 2016 the WHO Assembly defined a global strategy to combat viral hepatitis viruses, which seeks to eliminate these infections by 2030. The most important goals of this programme, adopted by 194 countries, are to reduce the incidence of viral hepatitis by 90 % and mortality rates – by 65 % as compared to the levels observed in 2016. Therefore, there is an obvious need for development of medicines for the treatment of chronic hepatitis C. The aim of the present paper was to determine basic approaches to planning pre-authorisation clinical trials for the main groups of medicines for the treatment of chronic hepatitis C. The paper summarises the current trends in the treatment of chronic hepatitis C; it lists medicines with direct antiviral effect that are currently registered in the Russian Federation, as well as interferon-free and interferon-containing regimens for the treatment of this disease. The authors examined the current requirements in force in the Russian Federation, namely: the Federal Law No. 61-FZ «On circulation of medicines» dated April 12, 2010, the Guideline on Evaluation of Medicinal Products, the Clinical Recommendations for Diagnosis and Treatment of Adult Patients with Hepatitis C, as well as recommendations of the European Medicines Agency and the Food and Drug Administration in order to analyse the planning of programmes of pre-authorisation clinical trials of interferon alfa products and direct antivirals.
{"title":"Planning a Programme of Pre-authorisation Clinical Trials of Medicines for the Treatment of Chronic Hepatitis C","authors":"A. Gubenko, N. Eremenko","doi":"10.30895/1991-2919-2019-9-1-6-13","DOIUrl":"https://doi.org/10.30895/1991-2919-2019-9-1-6-13","url":null,"abstract":"In 2016 the WHO Assembly defined a global strategy to combat viral hepatitis viruses, which seeks to eliminate these infections by 2030. The most important goals of this programme, adopted by 194 countries, are to reduce the incidence of viral hepatitis by 90 % and mortality rates – by 65 % as compared to the levels observed in 2016. Therefore, there is an obvious need for development of medicines for the treatment of chronic hepatitis C. The aim of the present paper was to determine basic approaches to planning pre-authorisation clinical trials for the main groups of medicines for the treatment of chronic hepatitis C. The paper summarises the current trends in the treatment of chronic hepatitis C; it lists medicines with direct antiviral effect that are currently registered in the Russian Federation, as well as interferon-free and interferon-containing regimens for the treatment of this disease. The authors examined the current requirements in force in the Russian Federation, namely: the Federal Law No. 61-FZ «On circulation of medicines» dated April 12, 2010, the Guideline on Evaluation of Medicinal Products, the Clinical Recommendations for Diagnosis and Treatment of Adult Patients with Hepatitis C, as well as recommendations of the European Medicines Agency and the Food and Drug Administration in order to analyse the planning of programmes of pre-authorisation clinical trials of interferon alfa products and direct antivirals. ","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91193832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-03-25DOI: 10.30895/1991-2919-2019-9-1-54-63
S. Moiseev, N. E. Kuz’mina, A. I. Luttseva
The work is a continuation of the research on the use of NMR spectroscopy in the quality control of natural peptide hormone-based active substances and their synthetic analogues.The aimof the paper was to develop identification test methods for triptorelin acetate and goserelin acetate substances using NMR spectroscopy that does not require reference standards ‒ with the aim of using the newly developed test methods in pharmacopoeial analysis.Materials and methods:the procedure was developed using two-dimensional NMR spectroscopy (1H-1H gCOSY,1H-13C gHSQC,1H-13C gHMBC).Results:thestudy made it possible to assign1H and13C NMR signals to a specific molecular fragment, and to determine the amino acid composition of each oligopeptide.Conclusions:the authors drew up a table showing structural assignment of NMR signals, which makes it possible to use the NMR method for identification testing of triptorelin acetate and goserelin acetate substances without the use of pharmacopoeial reference standards. The study helped to determine the optimal temperature conditions for recording13C NMR spectra (27 °С and 50 °С for triptorelin acetate and goserelin acetate, respectively). It was demonstrated that13C NMR spectroscopy could be used for identification testing in pharmacopoeial analysis.
{"title":"Development of Identification Test Methods for Triptorelin Acetate and Goserelin Acetate Substances using NMR spectroscopy","authors":"S. Moiseev, N. E. Kuz’mina, A. I. Luttseva","doi":"10.30895/1991-2919-2019-9-1-54-63","DOIUrl":"https://doi.org/10.30895/1991-2919-2019-9-1-54-63","url":null,"abstract":"The work is a continuation of the research on the use of NMR spectroscopy in the quality control of natural peptide hormone-based active substances and their synthetic analogues.The aimof the paper was to develop identification test methods for triptorelin acetate and goserelin acetate substances using NMR spectroscopy that does not require reference standards ‒ with the aim of using the newly developed test methods in pharmacopoeial analysis.Materials and methods:the procedure was developed using two-dimensional NMR spectroscopy (1H-1H gCOSY,1H-13C gHSQC,1H-13C gHMBC).Results:thestudy made it possible to assign1H and13C NMR signals to a specific molecular fragment, and to determine the amino acid composition of each oligopeptide.Conclusions:the authors drew up a table showing structural assignment of NMR signals, which makes it possible to use the NMR method for identification testing of triptorelin acetate and goserelin acetate substances without the use of pharmacopoeial reference standards. The study helped to determine the optimal temperature conditions for recording13C NMR spectra (27 °С and 50 °С for triptorelin acetate and goserelin acetate, respectively). It was demonstrated that13C NMR spectroscopy could be used for identification testing in pharmacopoeial analysis. ","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82966157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-03-25DOI: 10.30895/1991-2919-2019-9-1-28-33
D. P. Romodanovsky, N. Eremenko, D. Goryachev
There are no specific requirements and recommendations in the Russian Federation for evaluation of bioequivalence of modified-release medicinal products. Until recently, modified-release products were regulated in a similar manner as immediate-release products, which is unacceptable considering the active ingredient release profile and its pharmacokinetics. The modified release characteristics require a more complex approach to the assessment of equivalence of generic medicines as compared with the reference product. The number of parameters to be assessed and the scope of testing depend on many factors (release mechanism, specific features of the dosage form, linearity of pharmacokinetics, potential for ingredient accumulation, dependence on food intake, dose-dumping effects, and the number of dosage strengths to be registered). The aim of this paper was to develop recommendations for the national procedure of modified-release products authorisation based on the analysis of international regulatory experience in this field. The paper reviews the current European Medicines Agency (EMA) guidelines on evaluation of bioequivalence of generic modified-release dosage forms for oral use that were taken as a basis for the development of Eurasian Economic Union regulations on bioequivalence assessment. The analysis of the above-mentioned documents made it possible to develop recommendations for the national procedure of modified-release products authorisation. In the case of modified-release products for oral use it is recommended to perform bioequivalence studies by comparing the test product with the reference product. The authors developed a procedural algorithm for bioequivalence studies of modified-release medicinal products.
{"title":"Regulatory Requirements of the European Medicines Agency for Evaluation of Bioequivalence of Modified-release Medicinal Products","authors":"D. P. Romodanovsky, N. Eremenko, D. Goryachev","doi":"10.30895/1991-2919-2019-9-1-28-33","DOIUrl":"https://doi.org/10.30895/1991-2919-2019-9-1-28-33","url":null,"abstract":"There are no specific requirements and recommendations in the Russian Federation for evaluation of bioequivalence of modified-release medicinal products. Until recently, modified-release products were regulated in a similar manner as immediate-release products, which is unacceptable considering the active ingredient release profile and its pharmacokinetics. The modified release characteristics require a more complex approach to the assessment of equivalence of generic medicines as compared with the reference product. The number of parameters to be assessed and the scope of testing depend on many factors (release mechanism, specific features of the dosage form, linearity of pharmacokinetics, potential for ingredient accumulation, dependence on food intake, dose-dumping effects, and the number of dosage strengths to be registered). The aim of this paper was to develop recommendations for the national procedure of modified-release products authorisation based on the analysis of international regulatory experience in this field. The paper reviews the current European Medicines Agency (EMA) guidelines on evaluation of bioequivalence of generic modified-release dosage forms for oral use that were taken as a basis for the development of Eurasian Economic Union regulations on bioequivalence assessment. The analysis of the above-mentioned documents made it possible to develop recommendations for the national procedure of modified-release products authorisation. In the case of modified-release products for oral use it is recommended to perform bioequivalence studies by comparing the test product with the reference product. The authors developed a procedural algorithm for bioequivalence studies of modified-release medicinal products.","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89682384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-03-25DOI: 10.30895/1991-2919-2019-9-1-14-27
A. V. Dobrovolskiy
In recent years, there has been an increasing interest in the development of combination medicines (fixed drug combinations) containing two or more active ingredients in a single dosage form. Therefore, there is an urgent need to develop an optimal programme of pre-authorisation clinical trials for combination medicines. The aim of the paper was to summarise modern science-based approaches to clinical development of combination medicines and identify possible ways of their practical implementation, taking into account the requirements of the current legislation. The author reviewed scientific publications devoted to creation of fixed drug combinations and analysed the regulatory documents defining regulatory requirements for pre-authorisation clinical studies of medicines in the Eurasian Economic Union, the Russian Federation, and other countries. Based on the results of the analysis the author described the general regulatory requirements for planning clinical studies of combination medicines for the purpose of their subsequent authorisation in the Russian Federation (via the national procedure) and the Eurasian Economic Union (via the centralized procedure). The pre-authorisation clinical development programme should be designed individually for each combination medicine. The selection of an optimal clinical trial strategy will make it possible to obtain sufficient information on the efficacy and safety of a combination medicine for its subsequent authorisation.
{"title":"Approaches to Clinical Development of Combination Medicines in the Russian Federation and the Eurasian Economic Union in view of the Requirements of the Current Legislation","authors":"A. V. Dobrovolskiy","doi":"10.30895/1991-2919-2019-9-1-14-27","DOIUrl":"https://doi.org/10.30895/1991-2919-2019-9-1-14-27","url":null,"abstract":"In recent years, there has been an increasing interest in the development of combination medicines (fixed drug combinations) containing two or more active ingredients in a single dosage form. Therefore, there is an urgent need to develop an optimal programme of pre-authorisation clinical trials for combination medicines. The aim of the paper was to summarise modern science-based approaches to clinical development of combination medicines and identify possible ways of their practical implementation, taking into account the requirements of the current legislation. The author reviewed scientific publications devoted to creation of fixed drug combinations and analysed the regulatory documents defining regulatory requirements for pre-authorisation clinical studies of medicines in the Eurasian Economic Union, the Russian Federation, and other countries. Based on the results of the analysis the author described the general regulatory requirements for planning clinical studies of combination medicines for the purpose of their subsequent authorisation in the Russian Federation (via the national procedure) and the Eurasian Economic Union (via the centralized procedure). The pre-authorisation clinical development programme should be designed individually for each combination medicine. The selection of an optimal clinical trial strategy will make it possible to obtain sufficient information on the efficacy and safety of a combination medicine for its subsequent authorisation. ","PeriodicalId":22286,"journal":{"name":"The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89273554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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