<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">farmaec</journal-id><journal-title-group><journal-title xml:lang="en">FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology</journal-title><trans-title-group xml:lang="ru"><trans-title>ФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2070-4909</issn><issn pub-type="epub">2070-4933</issn><publisher><publisher-name>IRBIS LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.17749/2070-4909.2019.12.3.178-190</article-id><article-id custom-type="elpub" pub-id-type="custom">farmaec-299</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Original Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Оригинальные статьи</subject></subj-group></article-categories><title-group><article-title>Availability and Pharmacoeconomics of Insulin Therapy in Countries with the Largest Number of Diabetics</article-title><trans-title-group xml:lang="ru"><trans-title>Доступность и фармакоэкономика инсулиновой терапии в странах с наибольшим количеством больных диабетом</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пономаренко </surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Ponomarenko</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>руководитель проекта</p></bio><bio xml:lang="en"><p>Project Manager</p></bio><email xlink:type="simple">ponomarenko@t-online.de</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">СофиГен, Инсу-Фарма АГ<country>Германия</country></aff><aff xml:lang="en">SophiGen, Insu-Pharma AG<country>Germany</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>28</day><month>10</month><year>2019</year></pub-date><volume>12</volume><issue>3</issue><fpage>178</fpage><lpage>190</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Ponomarenko S.V., 2019</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="ru">Пономаренко  С.В.</copyright-holder><copyright-holder xml:lang="en">Ponomarenko S.V.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.pharmacoeconomics.ru/jour/article/view/299">https://www.pharmacoeconomics.ru/jour/article/view/299</self-uri><abstract><p>The aim of the review was to analyze the availability of insulin therapy and the ways to improve it in countries with the largest number of patients with diabetes. It was also aimed to assess the medical, social and economic importance of insulin therapy and industrial production of therapeutic recombinant insulin.</p><sec><title>Materials and methods</title><p>Materials and methods. The analysis was based on the data taken from monographs and publications in peer-reviewed journals, reports of companies and medical organizations, and the information available in the Internet. The demand and supply in the market of recombinant therapeutic insulin, the insulin market segmentation, and the costs for insulin replacement therapy in countries with the largest number of patients with diabetes were studied. </p></sec><sec><title>Results and discussion</title><p>Results and discussion. The pro- and contra- arguments regarding the import of insulin and its impact on the national budget are presented. Technological specifics of recombinant insulin production are discussed; the funding and investments in the biopharmaceutical sector are analyzed. The benefits of industrial production of recombinant therapeutic insulin and its impact on the regional and national economy are demonstrated.</p></sec><sec><title>Conclusion</title><p>Conclusion. The availability of therapeutic insulin in most countries with the largest number of diabetics is unsatisfactory and needs a radical improvement. By analyzing the economic aspects of diabetes and the pharmacoeconomics of insulin, it is advised to develop a modern management system for insulin replacement therapy, especially in countries with large numbers of diabetics. The use of innovative technologies will reduce the production costs of recombinant therapeutic insulin, increase the availability of insulin therapy and thereby improve the quality of life in diabetic patients. Evidence that the production of therapeutic insulin has a positive effect not only on the healthcare, but on the socio-economic situation in the region is also provided. Countries with a number of diabetics exceeding 5 million are encouraged to launch their own production of recombinant therapeutic insulin. The results of the present analysis confirm that half of them are able to manufacture adequate human insulin and/or its analogues.</p></sec><sec><title> </title><p> </p></sec></abstract><trans-abstract xml:lang="ru"><p>Цель – анализ доступности инсулиновой терапии и путей ее улучшения в странах с наибольшим количеством пациентов с диабетом. Проанализирована медико-социальная и политико-экономическая значимость инсулиновой терапии и промышленного производства препаратов рекомбинантного инсулина.</p><sec><title>Материалы и методы</title><p>Материалы и методы. Анализ проводился на основе данных монографий и публикаций в научных рецензируемых журналах, отчетов фармацевтических компаний и медицинских организаций, а также релевантной информации, размещенной в сети Интернет. Изучены спрос и предложение на рынке рекомбинантного инсулина, сегментация рынка инсулина и стоимость заместительной инсулиновой терапии в странах с наибольшим количеством больных сахарным диабетом. </p></sec><sec><title>Результаты и обсуждение</title><p>Результаты и обсуждение. Представлены аргументы в пользу и против импорта инсулина и его влияния на государственный бюджет. Обсуждаются технологические особенности производства рекомбинантного инсулина, анализируются финансирование и инвестиции в биофармацевтический сектор. Показаны преимущества промышленного производства препаратов рекомбинантного инсулина и его влияние на региональную и национальную экономику.</p></sec><sec><title>Заключение</title><p>Заключение. Доступность препаратов инсулина в большинстве стран с наибольшим количеством больных диабетом является неудовлетворительной и требует радикального улучшения. Анализ эпидимиологических, экономических аспектов диабета и фармакоэкономики инсулина подтверждает целесообразность разработки современной системы управления заместительной инсулинотерапией, особенно в странах с большим количеством больных диабетом. Использование инновационных технологий позволит снизить себестоимость производства препаратов рекомбинантного инсулина, повысить доступность инсулиновой терапии и тем самым продлить и улучшить качество жизни больных диабетом. В обзоре приведен пример того, что производство препаратов инсулина оказывает положительное влияние не только на здравоохранение, но и на социально-экономическую ситуацию в регионе. Странам, в которых число больных диабетом превышает 5 млн человек, рекомендуется начать собственное производство препаратов рекомбинантного инсулина. Результаты данного анализа подтверждают, что половина из них в состоянии начать производство адекватного количества человеческого инсулина и/или его аналогов.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>эпидемиология и фармакоэкономика сахарного диабета</kwd><kwd>препараты рекомбинантного инсулина</kwd><kwd>доступность и потребность инсулина</kwd><kwd>производство человеческого инсулина и его аналогов</kwd><kwd>QALY</kwd><kwd>анализ "затраты-эффективность" инсулиновой терапии</kwd><kwd>фармакоэкономика инсулина</kwd></kwd-group><kwd-group xml:lang="en"><kwd>epidemiology and pharmacoeconomics of diabetes mellitus</kwd><kwd>recombinant therapeutic insulin</kwd><kwd>its availability and need</kwd><kwd>production of human insulin and its analogues</kwd><kwd>QALY</kwd><kwd>cost-effectiveness analysis of insulin therapy</kwd><kwd>insulin pharmacoeconomics</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Guidelines on second- and third-line medicines and type of insulin for the control of blood glucose levels in non-pregnant adults with diabetes mellitus. Geneva: World Health Organization. 2018.</mixed-citation><mixed-citation xml:lang="en">Guidelines on second- and third-line medicines and type of insulin for the control of blood glucose levels in non-pregnant adults with diabetes mellitus. Geneva: World Health Organization. 2018.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Global report on diabetes. World Health Organization. Geneva. 2016.</mixed-citation><mixed-citation xml:lang="en">Global report on diabetes. World Health Organization. Geneva. 2016.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Textbook of diabetes (ed by: Holt R. I.G, Cockram C. S., Flyvbjerg A., Goldstein B. J.) Fifth edition. Wiley-Blackwell. 2017. 1104 p.</mixed-citation><mixed-citation xml:lang="en">Textbook of diabetes (ed by: Holt R. I.G, Cockram C. S., Flyvbjerg A., Goldstein B. J.) Fifth edition. Wiley-Blackwell. 2017. 1104 p.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes – 2019. American Diabetes Association. Diabetes Care. 2019; 42 (S1): S13-S28. DOI: https://doi.org/10.2337/dc19-S002.</mixed-citation><mixed-citation xml:lang="en">Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes – 2019. American Diabetes Association. Diabetes Care. 2019; 42 (S1): S13-S28. DOI: https://doi.org/10.2337/dc19-S002.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">IDF DIABETES ATLAS Eighth edition. International Diabetes Federation. 2017; [Electronic resource] URL: https://www. diabetesatlas.org. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">IDF DIABETES ATLAS Eighth edition. International Diabetes Federation. 2017; [Electronic resource] URL: https://www. diabetesatlas.org. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Crasto W., Jarvis J., Davies M. J. Handbook of Insulin Therapies. Springer. 2016; 209 p.</mixed-citation><mixed-citation xml:lang="en">Crasto W., Jarvis J., Davies M. J. Handbook of Insulin Therapies. Springer. 2016; 209 p.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Davies M. J., D’Alessio D.A., Fradkin j., Walter N. Kernan W. N., et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018; 41: 2669-2701. DOI: https://doi.org/10.2337/dci18-0033.</mixed-citation><mixed-citation xml:lang="en">Davies M. J., D’Alessio D.A., Fradkin j., Walter N. Kernan W. N., et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018; 41: 2669-2701. DOI: https://doi.org/10.2337/dci18-0033.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Landgraf W., Sandow J. Recombinant Human Insulins – Clinical Efficacy and Safety in Diabetes Therapy. European Endocrinology. 2015; 12 (1): 1-6. DOI: 10.17925/EE.2016.12.01.12.</mixed-citation><mixed-citation xml:lang="en">Landgraf W., Sandow J. Recombinant Human Insulins – Clinical Efficacy and Safety in Diabetes Therapy. European Endocrinology. 2015; 12 (1): 1-6. DOI: 10.17925/EE.2016.12.01.12.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Bommer C., Sagalova V., Heesemann E., et al. Global Economic Burden of Diabetes in Adults: Projections From 2015 to 2030. Diabetes Care. 2018; 41 (5): 963-970. DOI: https://doi.org/10.2337/dc17-1962.</mixed-citation><mixed-citation xml:lang="en">Bommer C., Sagalova V., Heesemann E., et al. Global Economic Burden of Diabetes in Adults: Projections From 2015 to 2030. Diabetes Care. 2018; 41 (5): 963-970. DOI: https://doi.org/10.2337/dc17-1962.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Cefallu W. T., Dawes D. E., Gavlak G., Goldman D., Herman W. H., et.al. Insulin Access and Affordability Working Group: Conclusions and Recommendations. Diabetes Care. 2018; 41 (6): 1299-1311. doi: 10.2337/dci18-0019.</mixed-citation><mixed-citation xml:lang="en">Cefallu W. T., Dawes D. E., Gavlak G., Goldman D., Herman W. H., et.al. Insulin Access and Affordability Working Group: Conclusions and Recommendations. Diabetes Care. 2018; 41 (6): 1299-1311. doi: 10.2337/dci18-0019.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Seuring T., Arachangel O., Suhrcke M. The economic costs of type 2 diabetes: A global systematic review. Pharm. Econ. 2015; 33: 811-831.</mixed-citation><mixed-citation xml:lang="en">Seuring T., Arachangel O., Suhrcke M. The economic costs of type 2 diabetes: A global systematic review. Pharm. Econ. 2015; 33: 811-831.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Beran D., Ewen M., Lepeska M., Laing R. Access to insulin: current challenges and constraints. Health Action International. 2017; [Electronic resource] URL: www.haiweb.org Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Beran D., Ewen M., Lepeska M., Laing R. Access to insulin: current challenges and constraints. Health Action International. 2017; [Electronic resource] URL: www.haiweb.org Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Ewen M, Joosse H-J, Beran D., Laing R. Insulin prices, availability and affordability in 13 low-income and middle-income countries. BMJ Global Health. 2019;4:e001410. [Electronic resource] URL: https://gh. bmj.com/content/bmjgh/4/3/e001410.full.pdf Accessed: 03.07.2019 doi:10.1136/bmjgh-2019-00141.</mixed-citation><mixed-citation xml:lang="en">Ewen M, Joosse H-J, Beran D., Laing R. Insulin prices, availability and affordability in 13 low-income and middle-income countries. BMJ Global Health. 2019;4:e001410. [Electronic resource] URL: https://gh. bmj.com/content/bmjgh/4/3/e001410.full.pdf Accessed: 03.07.2019 doi:10.1136/bmjgh-2019-00141.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Maier K.,Riley M.ImprovingInsulinAccessandAffordability/ADA 2018; 1-15. [Electronic resource] URL: http://www.diabetes.org/ assets/pdfs/advocacy/improving-insulin-access-and.pdf. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Maier K.,Riley M.ImprovingInsulinAccessandAffordability/ADA 2018; 1-15. [Electronic resource] URL: http://www.diabetes.org/ assets/pdfs/advocacy/improving-insulin-access-and.pdf. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">American Diabetes Association® Reaffirms Commitment to Insulin Access and Affordability for All – Transparency on Insulin Pricing Critical. 2018; [Electronic resource] URL: http://www.diabetes. org/newsroom/press-releases/2018/insulin-access-affordabilitytransparency-critical.html Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">American Diabetes Association® Reaffirms Commitment to Insulin Access and Affordability for All – Transparency on Insulin Pricing Critical. 2018; [Electronic resource] URL: http://www.diabetes. org/newsroom/press-releases/2018/insulin-access-affordabilitytransparency-critical.html Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Beran D. The Rapid Assessment Protocol for Insulin Access (RAPIA): Research for Action on Access to Diabetes Care RG2004. 2009; [Electronic resource] URL: https://www.researchgate.net/ publication/228381768. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Beran D. The Rapid Assessment Protocol for Insulin Access (RAPIA): Research for Action on Access to Diabetes Care RG2004. 2009; [Electronic resource] URL: https://www.researchgate.net/ publication/228381768. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Economic Costs of Diabetes in the U.S. in 2017. Diabetes Care. 2018; 41: 917-928. DOI: https://doi.org/10.2337/dci18-0007.</mixed-citation><mixed-citation xml:lang="en">Economic Costs of Diabetes in the U.S. in 2017. Diabetes Care. 2018; 41: 917-928. DOI: https://doi.org/10.2337/dci18-0007.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Pedron S., Emmert-Fees K., Laxy M., SchwettmannL. The impact of diabetes on labour market participation: a systematic review of results and methods. BMC Public Health. 2019; 19: 1-13. DOI: https://doi.org/10.1186/s12889-018-6324-6.</mixed-citation><mixed-citation xml:lang="en">Pedron S., Emmert-Fees K., Laxy M., SchwettmannL. The impact of diabetes on labour market participation: a systematic review of results and methods. BMC Public Health. 2019; 19: 1-13. DOI: https://doi.org/10.1186/s12889-018-6324-6.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Kähm K., Laxy M., Schneider U., Rogowski W.H., Lhachimi S.K., Holle R. Health care costs associated with incident complications in patients with type 2 diabetes in Germany. Diabetes Care. 2018; 41: 971-978. DOI: https://doi.org/10.2337/dc17-1763.</mixed-citation><mixed-citation xml:lang="en">Kähm K., Laxy M., Schneider U., Rogowski W.H., Lhachimi S.K., Holle R. Health care costs associated with incident complications in patients with type 2 diabetes in Germany. Diabetes Care. 2018; 41: 971-978. DOI: https://doi.org/10.2337/dc17-1763.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Mbanya J. C., Sandow J., Landgraf W., OwensD.R. Recombinant Human Insulin in Global Diabetes Management – Focus on Clinical Efficacy. European Endocrinology. 2017; 13 (1): 21-25. DOI: https:// doi.org/10.17925/EE.2017.13.01.21.</mixed-citation><mixed-citation xml:lang="en">Mbanya J. C., Sandow J., Landgraf W., OwensD.R. Recombinant Human Insulin in Global Diabetes Management – Focus on Clinical Efficacy. European Endocrinology. 2017; 13 (1): 21-25. DOI: https:// doi.org/10.17925/EE.2017.13.01.21.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Riddle M. C., Herman W. H. The Cost of Diabetes Cared An Elephant in the Room. Diabetes Care. 2018; 41: 929-932. DOI: https:// doi.org/10.2337/dci18-0012.</mixed-citation><mixed-citation xml:lang="en">Riddle M. C., Herman W. H. The Cost of Diabetes Cared An Elephant in the Room. Diabetes Care. 2018; 41: 929-932. DOI: https:// doi.org/10.2337/dci18-0012.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Ogurtsova K., J. D. Fernandes J. D., Huang Y., Linnenkamp U., et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Research and Clinical Practice. 2017; 128: 40-50.</mixed-citation><mixed-citation xml:lang="en">Ogurtsova K., J. D. Fernandes J. D., Huang Y., Linnenkamp U., et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Research and Clinical Practice. 2017; 128: 40-50.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Liebl A., Khunti K., Orozco-Beltran D., Yale J.-F. Health Economic Evaluation of Type 2 Diabetes Mellitus: A Clinical Practice Focused Review. Clinical Medicine Insights: Endocrinology and Diabetes. 2015; 8: 13-19. DOI:10.4137/CMED.S20906.</mixed-citation><mixed-citation xml:lang="en">Liebl A., Khunti K., Orozco-Beltran D., Yale J.-F. Health Economic Evaluation of Type 2 Diabetes Mellitus: A Clinical Practice Focused Review. Clinical Medicine Insights: Endocrinology and Diabetes. 2015; 8: 13-19. DOI:10.4137/CMED.S20906.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Petrides D. Bioprocess Design and Economics. Bioseparations Science and Engineering 2nd Edition (ed by: Harrison R. G., Todd P. W., Rudge S. R., Petrides D. P.). Oxford University Press. 2015; 11.1-11.83.</mixed-citation><mixed-citation xml:lang="en">Petrides D. Bioprocess Design and Economics. Bioseparations Science and Engineering 2nd Edition (ed by: Harrison R. G., Todd P. W., Rudge S. R., Petrides D. P.). Oxford University Press. 2015; 11.1-11.83.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Rotenstein K. S., Ran N. R., Shivers J. P., Yarchoan M., Close K. L. Opportunities and Challenges for Biosimilars: What’s on the Horizon in the Global Insulin Market? Clinical Diabetes. 2012; 30 (4): 138-150.</mixed-citation><mixed-citation xml:lang="en">Rotenstein K. S., Ran N. R., Shivers J. P., Yarchoan M., Close K. L. Opportunities and Challenges for Biosimilars: What’s on the Horizon in the Global Insulin Market? Clinical Diabetes. 2012; 30 (4): 138-150.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Wirtz V. J. Insulin Market Profile 2016. Amsterdam: Health Action International: 104 p. [Electronic resource] URL: https://haiweb. org/wp-content/uploads/2016/04/ACCISS_Insulin-Market-Profile_ FINAL.pdf. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Wirtz V. J. Insulin Market Profile 2016. Amsterdam: Health Action International: 104 p. [Electronic resource] URL: https://haiweb. org/wp-content/uploads/2016/04/ACCISS_Insulin-Market-Profile_ FINAL.pdf. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Assessment report EMA/CHMP/340840/2014. Abasria/ International non-proprietary name: insulin glargine Procedure No. EMEA/H/C/002835/0000. [Electronic resource] URL: https://www. ema.europa.eu/en/documents/assessment-report/abasria-eparpublic-assessment-report_en.pdf. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Assessment report EMA/CHMP/340840/2014. Abasria/ International non-proprietary name: insulin glargine Procedure No. EMEA/H/C/002835/0000. [Electronic resource] URL: https://www. ema.europa.eu/en/documents/assessment-report/abasria-eparpublic-assessment-report_en.pdf. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Mylan and Biocon Announce Regulatory Submission for Insulin Glargine Accepted for Review by European Medicines Agency 2016. [Electronic resource] URL: http://newsroom.mylan.com/2016-11-03-Mylan-and-Biocon-Announce-Regulatory-Submission-for-Insulin-Glargine-Accepted-for-Review-by-European-Medicines-Agency Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Mylan and Biocon Announce Regulatory Submission for Insulin Glargine Accepted for Review by European Medicines Agency 2016. [Electronic resource] URL: http://newsroom.mylan.com/2016-11-03-Mylan-and-Biocon-Announce-Regulatory-Submission-for-Insulin-Glargine-Accepted-for-Review-by-European-Medicines-Agency Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Merck Announces U. S. FDA Filing Acceptance of New Drug Application (NDA) for MK-1293, an Investigational Follow-On Biologic Insulin Glargine 2016. [Electronic resource] URL: https://www. mrknewsroom.com/news-release/research-and-development-news/ merck-announces-us-fda-filing-acceptance-new-drug-application Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Merck Announces U. S. FDA Filing Acceptance of New Drug Application (NDA) for MK-1293, an Investigational Follow-On Biologic Insulin Glargine 2016. [Electronic resource] URL: https://www. mrknewsroom.com/news-release/research-and-development-news/ merck-announces-us-fda-filing-acceptance-new-drug-application Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Ewen M., Joosse H.-J., Ashigbie P., Beran D., Laing R. Insulin Prices Profile. 2016: 155 p. Amsterdam: Health Action International. [Electronic resource] URL: www.haiweb.org. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Ewen M., Joosse H.-J., Ashigbie P., Beran D., Laing R. Insulin Prices Profile. 2016: 155 p. Amsterdam: Health Action International. [Electronic resource] URL: www.haiweb.org. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Kuhlmann M. K., Schmidt A. Production and manufacturing of biosimilar insulins: implications for patients, physicians, and health care systems. Biosimilars. 2014; 4: 45-48.</mixed-citation><mixed-citation xml:lang="en">Kuhlmann M. K., Schmidt A. Production and manufacturing of biosimilar insulins: implications for patients, physicians, and health care systems. Biosimilars. 2014; 4: 45-48.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Davies M., Dahl D., Heise T., Kiljanski J., Mathieu C. Introduction of biosimilar insulins in Europe. Diabet. Med. 2017; 34: 1340-1353.</mixed-citation><mixed-citation xml:lang="en">Davies M., Dahl D., Heise T., Kiljanski J., Mathieu C. Introduction of biosimilar insulins in Europe. Diabet. Med. 2017; 34: 1340-1353.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Sandow J., Landgraf W., Becker R., Seipke G. Equivalent Recombinant Human Insulin Preparations and their Place in Therapy Diabetes. European Endocrinology. 2015; 11 (1): DOI: 10.17925/ EE.2015.11.01.10.</mixed-citation><mixed-citation xml:lang="en">Sandow J., Landgraf W., Becker R., Seipke G. Equivalent Recombinant Human Insulin Preparations and their Place in Therapy Diabetes. European Endocrinology. 2015; 11 (1): DOI: 10.17925/ EE.2015.11.01.10.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Derwahl K. M., Bailey T. S., Wernicke-Panten K., Ping L., Pierre S. Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 2 Diabetes, Also Using Insulin Glargine: SORELLA 2 Study. DTT. 2018; 20 (1): DOI: 10.1089/dia.2017.0281.</mixed-citation><mixed-citation xml:lang="en">Derwahl K. M., Bailey T. S., Wernicke-Panten K., Ping L., Pierre S. Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 2 Diabetes, Also Using Insulin Glargine: SORELLA 2 Study. DTT. 2018; 20 (1): DOI: 10.1089/dia.2017.0281.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Owens D. R., Traylor L., Mullins P., Landgraf. W. Patient-level meta-analysis of efficacy and hypoglycaemia in people with type 2 diabetes initiating insulin glargine 100U/mL or neutral protamine Hagedorn insulin analysed according to concomitant oral antidiabetes therapy. Diabetes Res Clin Pract. 2017; 124: 57-65.</mixed-citation><mixed-citation xml:lang="en">Owens D. R., Traylor L., Mullins P., Landgraf. W. Patient-level meta-analysis of efficacy and hypoglycaemia in people with type 2 diabetes initiating insulin glargine 100U/mL or neutral protamine Hagedorn insulin analysed according to concomitant oral antidiabetes therapy. Diabetes Res Clin Pract. 2017; 124: 57-65.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Tieu C., Lucas E. J., DePaola M., Rosman L., Alexander G. C. Efficacy and safety of biosimilar insulins compared to their reference products: A systematic review. PLoS ONE 2018; 13(4): e0195012. [Electronic resource] URL: https://journals.plos.org/plosone/ article?id=10.1371/journal.pone.0195012. Accessed: 03.07.2019. DOI: https://doi.org/10.1371/journal.pone.0195012.</mixed-citation><mixed-citation xml:lang="en">Tieu C., Lucas E. J., DePaola M., Rosman L., Alexander G. C. Efficacy and safety of biosimilar insulins compared to their reference products: A systematic review. PLoS ONE 2018; 13(4): e0195012. [Electronic resource] URL: https://journals.plos.org/plosone/ article?id=10.1371/journal.pone.0195012. Accessed: 03.07.2019. DOI: https://doi.org/10.1371/journal.pone.0195012.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Hua X., Carvalho N., Tew M., et al. Expenditures and Prices of Antihyperglycemic Medications in the United States: 2002-2013. JAMA. 2016; 315 (13): 1400-1402. DOI:10.1001/jama.2016.0126.</mixed-citation><mixed-citation xml:lang="en">Hua X., Carvalho N., Tew M., et al. Expenditures and Prices of Antihyperglycemic Medications in the United States: 2002-2013. JAMA. 2016; 315 (13): 1400-1402. DOI:10.1001/jama.2016.0126.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Holden S. E., Poole C. D., Morgan C. L., Currie C. J. Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin. BMJ Open. 2011; 2: 1-7.</mixed-citation><mixed-citation xml:lang="en">Holden S. E., Poole C. D., Morgan C. L., Currie C. J. Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin. BMJ Open. 2011; 2: 1-7.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Heinemann L. Insulin Pens and New Ways of Insulin Delivery. DTT. 2013; 15: Supplement 1. S48-S59. DOI: 10.1089/dia.2013.1506.</mixed-citation><mixed-citation xml:lang="en">Heinemann L. Insulin Pens and New Ways of Insulin Delivery. DTT. 2013; 15: Supplement 1. S48-S59. DOI: 10.1089/dia.2013.1506.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Cafasso J. Insulin Prices: Pumps, Pens, Syringes, and More. 2018. [Electronic resource] URL: https://www.healthline.com/health/ type-2-diabetes/insulin-prices-pumps-pens-syringes Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Cafasso J. Insulin Prices: Pumps, Pens, Syringes, and More. 2018. [Electronic resource] URL: https://www.healthline.com/health/ type-2-diabetes/insulin-prices-pumps-pens-syringes Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Sorli C., Heile M. K. Identifying and meeting the challenges of insulin therapy in type 2 diabetes. J. Multidiscip. Healthcare. 2014; 7: 267-282.</mixed-citation><mixed-citation xml:lang="en">Sorli C., Heile M. K. Identifying and meeting the challenges of insulin therapy in type 2 diabetes. J. Multidiscip. Healthcare. 2014; 7: 267-282.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Russell-Jones D., Gall M.-A., Niemeyer M., Diamant M., Del Prato S. Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: a meta-analysis of seven clinical trials. Nutr Metab Cardiovasc Dis. 2015; 25: 898-905.</mixed-citation><mixed-citation xml:lang="en">Russell-Jones D., Gall M.-A., Niemeyer M., Diamant M., Del Prato S. Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: a meta-analysis of seven clinical trials. Nutr Metab Cardiovasc Dis. 2015; 25: 898-905.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Silva T.B.C., Almeida P.H.R.F., Araújo V.E., De Assis Acurcio F., et al. Effectiveness and safety of insulin glargine versus detemir analysis in patients with type 1 diabetes: systematic review and metaanalysis. Ther Adv Endocrinol Metab. 2018; 9(8): 241–254.</mixed-citation><mixed-citation xml:lang="en">Silva T.B.C., Almeida P.H.R.F., Araújo V.E., De Assis Acurcio F., et al. Effectiveness and safety of insulin glargine versus detemir analysis in patients with type 1 diabetes: systematic review and metaanalysis. Ther Adv Endocrinol Metab. 2018; 9(8): 241–254.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Hasslacher C., Bermejo J. L. Treatment with insulin analogs and prevalence of cardiovascular complications in patients with type 1 diabetes. Ther Adv Endocrinol Metab. 2017; 8 (11): 149-157. DOI: 10.1177/2042018817732732.</mixed-citation><mixed-citation xml:lang="en">Hasslacher C., Bermejo J. L. Treatment with insulin analogs and prevalence of cardiovascular complications in patients with type 1 diabetes. Ther Adv Endocrinol Metab. 2017; 8 (11): 149-157. DOI: 10.1177/2042018817732732.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Bjekic´-Macut J., Zˇivkovic´ T.B., Kocic R. Clinical Benefit of Basal Insulin Analogue Treatment in Persons with Type 2 Diabetes Inadequately Controlled on Prior Insulin Therapy: A Prospective, Noninterventional, Multicenter Study. Diabetes Ther. 2018; 9: 651-662. https://doi.org/10.1007/s13300-018-0378-4.</mixed-citation><mixed-citation xml:lang="en">Bjekic´-Macut J., Zˇivkovic´ T.B., Kocic R. Clinical Benefit of Basal Insulin Analogue Treatment in Persons with Type 2 Diabetes Inadequately Controlled on Prior Insulin Therapy: A Prospective, Noninterventional, Multicenter Study. Diabetes Ther. 2018; 9: 651-662. https://doi.org/10.1007/s13300-018-0378-4.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Tricco A. C., Ashoor H. M., Antony J., Beyene J., et al. Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis. BMJ. 2014; 349: g5459. [Electronic resource] URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847127/ pdf/2046-4053-2-73.pdf. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Tricco A. C., Ashoor H. M., Antony J., Beyene J., et al. Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis. BMJ. 2014; 349: g5459. [Electronic resource] URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847127/ pdf/2046-4053-2-73.pdf. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">The Economic Impact of the U. S. Biopharmaceutical Industry: 2015 National and State Estimates. PhRMA_GoBOLDLY. 2017; Pharmaceutical Research and Manufacturers of America (PhRMA) special 301 submissial 2018. Washington, DC: PhRMA. 179 p.</mixed-citation><mixed-citation xml:lang="en">The Economic Impact of the U. S. Biopharmaceutical Industry: 2015 National and State Estimates. PhRMA_GoBOLDLY. 2017; Pharmaceutical Research and Manufacturers of America (PhRMA) special 301 submissial 2018. Washington, DC: PhRMA. 179 p.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Gurramkonda C., Polez S., Skoko N., Adnan A., Gabel T., et al. Application of simple fed-batch technique to high-level secretory production of insulin precursor using Pichia pastoris with subsequent purification and conversion to human insulin. Microbial Cell Factories. 2010; 9: 31-42. http://www.microbialcellfactories. com/content/9/1/31</mixed-citation><mixed-citation xml:lang="en">Gurramkonda C., Polez S., Skoko N., Adnan A., Gabel T., et al. Application of simple fed-batch technique to high-level secretory production of insulin precursor using Pichia pastoris with subsequent purification and conversion to human insulin. Microbial Cell Factories. 2010; 9: 31-42. http://www.microbialcellfactories. com/content/9/1/31</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Kroeff E. P., Owenes R. A., Campbell E. L., Johnson R. D., Marks H. I. Production scale purification of biosynthetic human insulin by reversed-phase high-performance liquid chromatography. Journal of Chromatography. 1989; 461: 45-61</mixed-citation><mixed-citation xml:lang="en">Kroeff E. P., Owenes R. A., Campbell E. L., Johnson R. D., Marks H. I. Production scale purification of biosynthetic human insulin by reversed-phase high-performance liquid chromatography. Journal of Chromatography. 1989; 461: 45-61</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Petrides D., Sapidou E., Calandranis J. Computer-Aided Process Analysis and Economic Evaluation for Biosynthetic Human Insulin Production – A Case Study. Biotechnol Bioeng. 1995; 48 (5): 529-541.</mixed-citation><mixed-citation xml:lang="en">Petrides D., Sapidou E., Calandranis J. Computer-Aided Process Analysis and Economic Evaluation for Biosynthetic Human Insulin Production – A Case Study. Biotechnol Bioeng. 1995; 48 (5): 529-541.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Krämer I., Sauer T. The new world of biosimilars: what diabetologists need to know about biosimilar insulins. British Journal of Diabetes &amp; Vascular Disease. 2010; 10: 163-171.</mixed-citation><mixed-citation xml:lang="en">Krämer I., Sauer T. The new world of biosimilars: what diabetologists need to know about biosimilar insulins. British Journal of Diabetes &amp; Vascular Disease. 2010; 10: 163-171.</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Nilsson J., Jonasson P., Samuelsson E., Stähl S., Uhlen M. Integrated production of human insulin and its C-peptide. Journal of Biotechnology. 1996; 48: 241-250.</mixed-citation><mixed-citation xml:lang="en">Nilsson J., Jonasson P., Samuelsson E., Stähl S., Uhlen M. Integrated production of human insulin and its C-peptide. Journal of Biotechnology. 1996; 48: 241-250.</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Gallegos J. E., Boyer C., Pauwels E., Kaplan W. A., Peccoud J. The Open Insulin Project: A Case Study for ‘Biohacked’ Medicines. Trends in Biotechnology. 2018; 36 (12): 1211-1218. DOI: https://doi. org/10.1016/j.tibtech.2018.07.009.</mixed-citation><mixed-citation xml:lang="en">Gallegos J. E., Boyer C., Pauwels E., Kaplan W. A., Peccoud J. The Open Insulin Project: A Case Study for ‘Biohacked’ Medicines. Trends in Biotechnology. 2018; 36 (12): 1211-1218. DOI: https://doi. org/10.1016/j.tibtech.2018.07.009.</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Baeshen N. A., Baeshen M. N., Sheikh A., Bora R. S., et al. Cell factories for insulin production. Microbial Cell Factories. 2014; 13: 141-149. http://www.microbialcellfactories.com/content/13/1/141.</mixed-citation><mixed-citation xml:lang="en">Baeshen N. A., Baeshen M. N., Sheikh A., Bora R. S., et al. Cell factories for insulin production. Microbial Cell Factories. 2014; 13: 141-149. http://www.microbialcellfactories.com/content/13/1/141.</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Polez S., Origi D., Zahariev S., Guarnaccia C., Tisminetzky S. G., Skoko N., Baralle M. A Simplified and Efficient Process for Insulin Production in Pichia pastoris. PLOS ONE. 2016; 11 (12): 1-15.</mixed-citation><mixed-citation xml:lang="en">Polez S., Origi D., Zahariev S., Guarnaccia C., Tisminetzky S. G., Skoko N., Baralle M. A Simplified and Efficient Process for Insulin Production in Pichia pastoris. PLOS ONE. 2016; 11 (12): 1-15.</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Petrides D. P., Koulouris A., Lagonikos P. T. The Role of Process Simulation in Pharmaceutical Process Development and Product Commercialization. Ispe pharmaceutical engineering®. 2002; 22 (1): 1-8.</mixed-citation><mixed-citation xml:lang="en">Petrides D. P., Koulouris A., Lagonikos P. T. The Role of Process Simulation in Pharmaceutical Process Development and Product Commercialization. Ispe pharmaceutical engineering®. 2002; 22 (1): 1-8.</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing. (Ed by Mollah H., Baseman H., Long M. John Wiley &amp; Sons, Inc. 2013; 416 p.</mixed-citation><mixed-citation xml:lang="en">Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing. (Ed by Mollah H., Baseman H., Long M. John Wiley &amp; Sons, Inc. 2013; 416 p.</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Gulf Pharmaceutical Industries (Julphar) Insulin Production Facility. [Electronic resource] URL: https://www.pharmaceuticaltechnology.com/projects/gulf-pharmaceutical-industries-julpharinsulin-production-facility-uae/. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Gulf Pharmaceutical Industries (Julphar) Insulin Production Facility. [Electronic resource] URL: https://www.pharmaceuticaltechnology.com/projects/gulf-pharmaceutical-industries-julpharinsulin-production-facility-uae/. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Patent WO 2012/098009. Chimeric Polypeptide comprising a Membrane Protein and an Insulin Precursor. Ponomarenko S. Applicant GlucoMetrix AG. Priority Date: 21.01.2011; International Filling: 20.01.2012 PCT/EP2012/000266.</mixed-citation><mixed-citation xml:lang="en">Patent WO 2012/098009. Chimeric Polypeptide comprising a Membrane Protein and an Insulin Precursor. Ponomarenko S. Applicant GlucoMetrix AG. Priority Date: 21.01.2011; International Filling: 20.01.2012 PCT/EP2012/000266.</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Kaplan W., Beall R. Insulin Patent Profile. Amsterdam: Health Action International. 2016.</mixed-citation><mixed-citation xml:lang="en">Kaplan W., Beall R. Insulin Patent Profile. Amsterdam: Health Action International. 2016.</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Rasmussen B. Innovation and Commercialisation in the Biopharmaceutical Industry: Creating and Capturing Value. Edward Elgar Publishing Ltd. 2010; 326 p.</mixed-citation><mixed-citation xml:lang="en">Rasmussen B. Innovation and Commercialisation in the Biopharmaceutical Industry: Creating and Capturing Value. Edward Elgar Publishing Ltd. 2010; 326 p.</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Anderlei T., Eibl D., Eibl R., Eisenkrätzer D. Facility of the Future. 2017. Dehema. 35 p.</mixed-citation><mixed-citation xml:lang="en">Anderlei T., Eibl D., Eibl R., Eisenkrätzer D. Facility of the Future. 2017. Dehema. 35 p.</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Lütke-Eversloh T., Rogge P. Biopharmaceutical manufacturing in single-use Bioreactors. Current status and challenges from a CDMO perspective. Pharm. Ind. 2018; 80 (2): 281-284.</mixed-citation><mixed-citation xml:lang="en">Lütke-Eversloh T., Rogge P. Biopharmaceutical manufacturing in single-use Bioreactors. Current status and challenges from a CDMO perspective. Pharm. Ind. 2018; 80 (2): 281-284.</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Gotham D., Barber M. J., Hill A. Production costs and potential prices for biosimilars of human insulin and insulin analogues. BMJ Glob Health. 2018; 3:e000850. [Electronic resource] URL: https://gh.bmj.com/content/bmjgh/3/5/e000850.full.pdf. Accessed: 03.07.2019. doi: 10.1136/bmjgh-2018-000850.</mixed-citation><mixed-citation xml:lang="en">Gotham D., Barber M. J., Hill A. Production costs and potential prices for biosimilars of human insulin and insulin analogues. BMJ Glob Health. 2018; 3:e000850. [Electronic resource] URL: https://gh.bmj.com/content/bmjgh/3/5/e000850.full.pdf. Accessed: 03.07.2019. doi: 10.1136/bmjgh-2018-000850.</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Seidenader N. Trend &amp; market report. Insights into the diabetes- &amp; insulin market. Brainnovative Consulting e.V. 2016; 32 p.</mixed-citation><mixed-citation xml:lang="en">Seidenader N. Trend &amp; market report. Insights into the diabetes- &amp; insulin market. Brainnovative Consulting e.V. 2016; 32 p.</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Lee J. PEST and NET analysis of biopharmaceutical industry. ICI Meeting 2015. [Electronic resource] URL: http://2015.icimeeting.com/ e-posters/pdf/22.pdf. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Lee J. PEST and NET analysis of biopharmaceutical industry. ICI Meeting 2015. [Electronic resource] URL: http://2015.icimeeting.com/ e-posters/pdf/22.pdf. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Fernandes J., Zhang P. COST-EFFECTIVE AND COST-SAVING INTERVENTIONS FOR PREVENTION AND CONTROL OF DIABETES. Diabetes Voice. 2016; 62 (2): 16-20.</mixed-citation><mixed-citation xml:lang="en">Fernandes J., Zhang P. COST-EFFECTIVE AND COST-SAVING INTERVENTIONS FOR PREVENTION AND CONTROL OF DIABETES. Diabetes Voice. 2016; 62 (2): 16-20.</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru">Pease A., Lo C., Earnest A., Liew D., Zoungas S. Evaluating optimal utilization of technology in type 1 diabetes mellitus from a clinical and health economic perspective: protocol for a systematic review. Systematic Reviews. 2018; 7: 44. DOI: https://doi.org/10.1186/ s13643-018-0706-9</mixed-citation><mixed-citation xml:lang="en">Pease A., Lo C., Earnest A., Liew D., Zoungas S. Evaluating optimal utilization of technology in type 1 diabetes mellitus from a clinical and health economic perspective: protocol for a systematic review. Systematic Reviews. 2018; 7: 44. DOI: https://doi.org/10.1186/ s13643-018-0706-9</mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Ourth H., Nelson J., Spoutz P., Morreale A. P. Development of a Pharmacoeconomic Model to Demonstrate the Effect of Clinical Pharmacist Involvement in Diabetes Management. J Manag Care Spec Pharm. 2018; 24 (5): 449-457.</mixed-citation><mixed-citation xml:lang="en">Ourth H., Nelson J., Spoutz P., Morreale A. P. Development of a Pharmacoeconomic Model to Demonstrate the Effect of Clinical Pharmacist Involvement in Diabetes Management. J Manag Care Spec Pharm. 2018; 24 (5): 449-457.</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru">Keeney E., Dawoud D., Dias S. Different Methods for Modelling Severe Hypoglycaemic Events: Implications for Effectiveness, Costs</mixed-citation><mixed-citation xml:lang="en">Keeney E., Dawoud D., Dias S. Different Methods for Modelling Severe Hypoglycaemic Events: Implications for Effectiveness, Costs</mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">and Health Utilities. PharmacoEconomics. 2018; 36: 523-532. DOI: https://doi.org/10.1007/s40273-018-0612-y.</mixed-citation><mixed-citation xml:lang="en">and Health Utilities. PharmacoEconomics. 2018; 36: 523-532. DOI: https://doi.org/10.1007/s40273-018-0612-y.</mixed-citation></citation-alternatives></ref><ref id="cit72"><label>72</label><citation-alternatives><mixed-citation xml:lang="ru">Bailey T. S., Walsh J., Stone J. Y. Emerging Technologies for Diabetes Care. DTT. 2018; 20 (S 2): S2.78-S2.84.</mixed-citation><mixed-citation xml:lang="en">Bailey T. S., Walsh J., Stone J. Y. Emerging Technologies for Diabetes Care. DTT. 2018; 20 (S 2): S2.78-S2.84.</mixed-citation></citation-alternatives></ref><ref id="cit73"><label>73</label><citation-alternatives><mixed-citation xml:lang="ru">Lawton J., Blackburn M., Rankin D., Allen J., Campbell F, et al. Research: Educational and Psychlogical Aspects The impact of using a closed-loop system on food choices: a qualitative study involving adults, teenagers and parents. Diabet. Med. 2019; 36; 753-760. DOI: 10.1111/dme 13887.</mixed-citation><mixed-citation xml:lang="en">Lawton J., Blackburn M., Rankin D., Allen J., Campbell F, et al. Research: Educational and Psychlogical Aspects The impact of using a closed-loop system on food choices: a qualitative study involving adults, teenagers and parents. Diabet. Med. 2019; 36; 753-760. DOI: 10.1111/dme 13887.</mixed-citation></citation-alternatives></ref><ref id="cit74"><label>74</label><citation-alternatives><mixed-citation xml:lang="ru">Bekiari E., Kitsios K., Thabit H., Tauschmann M., et al. Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis. BMJ. 2018; 361: k1310. [Electronic resource] URL: http://dx.doi.org/10.1136/bmj.k1310. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Bekiari E., Kitsios K., Thabit H., Tauschmann M., et al. Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis. BMJ. 2018; 361: k1310. [Electronic resource] URL: http://dx.doi.org/10.1136/bmj.k1310. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit75"><label>75</label><citation-alternatives><mixed-citation xml:lang="ru">Rege N. K., Wickramasinghe N. P., Tustan A. N., Phillips N. F.B., Yee V. C., Ismail-Beigi F., Weiss M. A. Structure-Based Stabilization of Insulin as a Therapeutic Protein Assembly via Enhanced Aromatic-Aromatic Interactions. J Biol.Chem. 2018; 293: [Electronic resource] URL: http://www.jbc.org/content/293/28/10895. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Rege N. K., Wickramasinghe N. P., Tustan A. N., Phillips N. F.B., Yee V. C., Ismail-Beigi F., Weiss M. A. Structure-Based Stabilization of Insulin as a Therapeutic Protein Assembly via Enhanced Aromatic-Aromatic Interactions. J Biol.Chem. 2018; 293: [Electronic resource] URL: http://www.jbc.org/content/293/28/10895. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit76"><label>76</label><citation-alternatives><mixed-citation xml:lang="ru">Zaykov A. N., Mayer J. P., DiMarchi R. D. Pursuit of a perfect insulin. Nature Rev. Drug Discovery. 2016; 15: 425-439.</mixed-citation><mixed-citation xml:lang="en">Zaykov A. N., Mayer J. P., DiMarchi R. D. Pursuit of a perfect insulin. Nature Rev. Drug Discovery. 2016; 15: 425-439.</mixed-citation></citation-alternatives></ref><ref id="cit77"><label>77</label><citation-alternatives><mixed-citation xml:lang="ru">Mikiewicz D., Bierczynska-Krzysik A., Sobolewska A., Stadnik D., Bogiel M., et al. Soluble Insulin Analogs Combining Rapid and Long-acting Hypoglycemic Properties – From an Efficient E. coli Expression System to a Pharmaceutical Formulation. PLoS One. 2017; 12 (3): e0172600. [Electronic resource] URL: https://journals.plos.org/ plosone/article?id=10.1371/journal.pone.0172600. Accessed: 03.07.2019. DOI: 10.1371/journal.pone.0172600.</mixed-citation><mixed-citation xml:lang="en">Mikiewicz D., Bierczynska-Krzysik A., Sobolewska A., Stadnik D., Bogiel M., et al. Soluble Insulin Analogs Combining Rapid and Long-acting Hypoglycemic Properties – From an Efficient E. coli Expression System to a Pharmaceutical Formulation. PLoS One. 2017; 12 (3): e0172600. [Electronic resource] URL: https://journals.plos.org/ plosone/article?id=10.1371/journal.pone.0172600. Accessed: 03.07.2019. DOI: 10.1371/journal.pone.0172600.</mixed-citation></citation-alternatives></ref><ref id="cit78"><label>78</label><citation-alternatives><mixed-citation xml:lang="ru">Patent WO 2012/048856 A1. Proinsulin with helper sequence. Ponomarenko S., Hermann S., Eckert K. Applicant GlucoMetrix AG. Priority Date: 12.10.2010; International Filling: 11.10.2011 PCT/ EP2011/005090.</mixed-citation><mixed-citation xml:lang="en">Patent WO 2012/048856 A1. Proinsulin with helper sequence. Ponomarenko S., Hermann S., Eckert K. Applicant GlucoMetrix AG. Priority Date: 12.10.2010; International Filling: 11.10.2011 PCT/ EP2011/005090.</mixed-citation></citation-alternatives></ref><ref id="cit79"><label>79</label><citation-alternatives><mixed-citation xml:lang="ru">Hwang H.G, Kim K.-J., Lee S.-H., Kim C.-K., et al. Recombinant glargine insulin production process using Escherichia coli. JMB. 2016; 10: 1781-1789.</mixed-citation><mixed-citation xml:lang="en">Hwang H.G, Kim K.-J., Lee S.-H., Kim C.-K., et al. Recombinant glargine insulin production process using Escherichia coli. JMB. 2016; 10: 1781-1789.</mixed-citation></citation-alternatives></ref><ref id="cit80"><label>80</label><citation-alternatives><mixed-citation xml:lang="ru">Sreenivas S., Krishnaiah S. M., Govindappa N., Basavaragu Y., et al. Enhancement in production of recombinant two-chain insulin glargine by over-expression of Kex2 protease in Pichia pastoris. Appl. Microbiol. Biotechn. 2015; 99(1): 327-336. [Electronic resource] URL: DOI 10.1007/s 00253-014-6052-5. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Sreenivas S., Krishnaiah S. M., Govindappa N., Basavaragu Y., et al. Enhancement in production of recombinant two-chain insulin glargine by over-expression of Kex2 protease in Pichia pastoris. Appl. Microbiol. Biotechn. 2015; 99(1): 327-336. [Electronic resource] URL: DOI 10.1007/s 00253-014-6052-5. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit81"><label>81</label><citation-alternatives><mixed-citation xml:lang="ru">High-throughput process development and scale-up of an intermediate purification step for recombinant insulin. GE Healthcare Life Sciences. [Electronic resource] URL: http://www. processdevelopmentforum.com/articles/high-throughput-processdevelopment-and-scale-up-of-an-intermediate-purification-step-forrecombinant-insulin/. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">High-throughput process development and scale-up of an intermediate purification step for recombinant insulin. GE Healthcare Life Sciences. [Electronic resource] URL: http://www. processdevelopmentforum.com/articles/high-throughput-processdevelopment-and-scale-up-of-an-intermediate-purification-step-forrecombinant-insulin/. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit82"><label>82</label><citation-alternatives><mixed-citation xml:lang="ru">Kim C.-K., Lee S.-B., Son Y.-J. Large-Scale Refolding and Ezyme Reaction of Human Preproinuslin for Production of Human Insulin. J Microbiol Biotechnol. 2015; 25 (10): 1742-1750. Doi: http:// dx.doi.org/10.4014/jmb.1504.04062.</mixed-citation><mixed-citation xml:lang="en">Kim C.-K., Lee S.-B., Son Y.-J. Large-Scale Refolding and Ezyme Reaction of Human Preproinuslin for Production of Human Insulin. J Microbiol Biotechnol. 2015; 25 (10): 1742-1750. Doi: http:// dx.doi.org/10.4014/jmb.1504.04062.</mixed-citation></citation-alternatives></ref><ref id="cit83"><label>83</label><citation-alternatives><mixed-citation xml:lang="ru">Chen Y., Wang Q., et al. Improving the refolding efficiency for proinsulin aspart inclusion body with optimized buffer compositions. Protein Expression and Purification. 2016; 122: 1-7.</mixed-citation><mixed-citation xml:lang="en">Chen Y., Wang Q., et al. Improving the refolding efficiency for proinsulin aspart inclusion body with optimized buffer compositions. Protein Expression and Purification. 2016; 122: 1-7.</mixed-citation></citation-alternatives></ref><ref id="cit84"><label>84</label><citation-alternatives><mixed-citation xml:lang="ru">Gusarov D., Nekipelova V., Gusarova V., Lasman V., Bairamashvili D. Displacement effect during HPLC preparative purification of human insulin. J Chromatogr Analyt Technol Biomed Life Sci. 2009; 87 (7): 1216-1220.</mixed-citation><mixed-citation xml:lang="en">Gusarov D., Nekipelova V., Gusarova V., Lasman V., Bairamashvili D. Displacement effect during HPLC preparative purification of human insulin. J Chromatogr Analyt Technol Biomed Life Sci. 2009; 87 (7): 1216-1220.</mixed-citation></citation-alternatives></ref><ref id="cit85"><label>85</label><citation-alternatives><mixed-citation xml:lang="ru">Nanev C., Petrov K. P. Steering a crystallization process to reduce crystal polydispersity; case study of insulin crystallization. Journal of Crystal Growth. 2017; 480: 164-169.</mixed-citation><mixed-citation xml:lang="en">Nanev C., Petrov K. P. Steering a crystallization process to reduce crystal polydispersity; case study of insulin crystallization. Journal of Crystal Growth. 2017; 480: 164-169.</mixed-citation></citation-alternatives></ref><ref id="cit86"><label>86</label><citation-alternatives><mixed-citation xml:lang="ru">Rege N. K., Weiss M. A., Phillips N. F.B. Development of Glucose-Responsive “Smart” Insulin Systems. Curr Opin Endocrinol Diabetes Obes. 2017; 24 (4): 267-278. DOI: 10.1097/MED.</mixed-citation><mixed-citation xml:lang="en">Rege N. K., Weiss M. A., Phillips N. F.B. Development of Glucose-Responsive “Smart” Insulin Systems. Curr Opin Endocrinol Diabetes Obes. 2017; 24 (4): 267-278. DOI: 10.1097/MED.</mixed-citation></citation-alternatives></ref><ref id="cit87"><label>87</label><citation-alternatives><mixed-citation xml:lang="ru">Bally L., Thabit H., Kojzar H., Mader J. K., et al. Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomized, crossover study. Lanzet Diabetes Endocrin. 2017; 5: 261-270.</mixed-citation><mixed-citation xml:lang="en">Bally L., Thabit H., Kojzar H., Mader J. K., et al. Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomized, crossover study. Lanzet Diabetes Endocrin. 2017; 5: 261-270.</mixed-citation></citation-alternatives></ref><ref id="cit88"><label>88</label><citation-alternatives><mixed-citation xml:lang="ru">Thueer T., Birkhaeuer L., Reilly D. Development of an advanced injection time model for an autoinjector. Med. Devices:Evid. Research. 2018; 11: 215-224.</mixed-citation><mixed-citation xml:lang="en">Thueer T., Birkhaeuer L., Reilly D. Development of an advanced injection time model for an autoinjector. Med. Devices:Evid. Research. 2018; 11: 215-224.</mixed-citation></citation-alternatives></ref><ref id="cit89"><label>89</label><citation-alternatives><mixed-citation xml:lang="ru">Lange J., Urbanek L., Burren S. Development of devices for selfinjection: using tribological analysis to optimize injection force. Med. Devices:Evid. Research. 2016; 9: 93-103.</mixed-citation><mixed-citation xml:lang="en">Lange J., Urbanek L., Burren S. Development of devices for selfinjection: using tribological analysis to optimize injection force. Med. Devices:Evid. Research. 2016; 9: 93-103.</mixed-citation></citation-alternatives></ref><ref id="cit90"><label>90</label><citation-alternatives><mixed-citation xml:lang="ru">Dadlani V., Pinsker, J.E., Dassau E., C. Kudva, Y. C. Advances in Closed-Loop Insulin Delivery Systems in Patients with Type 1 Diabetes. Current Diabetes Reports. 2018; 18 (10): [Electronic resource] URL: 18. 10.1007/s11892-018-1051-z. Accessed: 03.07.2019.</mixed-citation><mixed-citation xml:lang="en">Dadlani V., Pinsker, J.E., Dassau E., C. Kudva, Y. C. Advances in Closed-Loop Insulin Delivery Systems in Patients with Type 1 Diabetes. Current Diabetes Reports. 2018; 18 (10): [Electronic resource] URL: 18. 10.1007/s11892-018-1051-z. Accessed: 03.07.2019.</mixed-citation></citation-alternatives></ref><ref id="cit91"><label>91</label><citation-alternatives><mixed-citation xml:lang="ru">Gedawy A., Martinez J., Al-Salami H., Dass C. R. Oral insulin delivery: existing barriers and current counter-strategies. JPP. 2017; 70: 197-213. DOI: 10.1111/jphp.12852.</mixed-citation><mixed-citation xml:lang="en">Gedawy A., Martinez J., Al-Salami H., Dass C. R. Oral insulin delivery: existing barriers and current counter-strategies. JPP. 2017; 70: 197-213. DOI: 10.1111/jphp.12852.</mixed-citation></citation-alternatives></ref><ref id="cit92"><label>92</label><citation-alternatives><mixed-citation xml:lang="ru">Ponomarenko S. V., Chshankin M. A. Impact of economic and medico-social factors on accessibility of insulin therapy for patients with diabetes mellitus in the CIS countries. Russian Journal of Biopharmaceuticals. 2018; 10 (6): P. 3-11.</mixed-citation><mixed-citation xml:lang="en">Ponomarenko S. V., Chshankin M. A. Impact of economic and medico-social factors on accessibility of insulin therapy for patients with diabetes mellitus in the CIS countries. Russian Journal of Biopharmaceuticals. 2018; 10 (6): P. 3-11.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
