References

diaendo

Сахарный диабет

Diabetes mellitus

2072-03512072-0378

Endocrinology research centre

10.14341/2072-0351-5825

diaendo-5825

Research Article

Статьи

Articles

Биосимиляры: презумпция виновности?.

Biosimilars: presumption of guilt

Шестакова

Марина Владимировна

Shestakova

Marina Vladimirovna

Викулова

Ольга Константиновна

Vikulova

Olga Konstantinovna

olga-vikulova-1973@yandex.ru

ФГБУ Эндокринологический научный центр, МоскваEndocrinology Research Centre, Moscow

2011

15122011

144

№4 (2011)

9199

2011

Шестакова М.В., Викулова О.К.

Shestakova M.V., Vikulova O.K.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.dia-endojournals.ru/jour/article/view/5825

Многие хронические системные заболевания, в том числе сахарный диабет, требуют пожизненного применения биотехнологических ле-карственных средств, от качества, эффетивности и безопасности которых зависят продолжительность и качество жизни пациентов.Окончание срока патентной защиты на многие оригинальные биопрепараты стало ключевым фактором разработки и широкого выходана фармацевтический рынок биосимиляров, которые представляют собой воспроизведенные версии оригинальных биотехнологическихсредств. Вследствие сложности структуры биологических продуктов и невозможности точного воспроизведения технологии производ-ства, поскольку она патентуется производителями брендов, биосимиляры не являются идентичной копией оригинального препарата.Несмотря на множество свидетельств терапевтической неэквивалентности, существует опасность ?автоматического? замещенияоригинальных препаратов на биосимиляры в связи с более низкой стоимостью и отсутствием в России законодательных мер, регла-ментирующих их регистрацию и обращение. Настоящая статья содержит детальную характеристику биосимиляров и обзор основныхпроблем, связанных с их использованием: аспекты контроля качества, несоответствия оригинальным биопрепаратам по эффектив-ности и безопасности, требования к проведению клинических исследований, процедуре регистрации и последующему фармаконадзорубезопасности терапии.

Some chronic systemic diseases, including diabetes mellitus, require the life-long use of biotechnological medical products, of which quality,effectiveness and safety depends the duration and quality of life for patients.Patent protection expiry of many original biological agents has assumed the key role in development of biosimilars (replica versions of originalbiotechnological products) and their broad entrance to the pharmaceutical market. Because of structural complexity of biological products andimpossibility of precise reproduction of patented processing, biosimilars are not ideal duplicates of original substances. Despite numerous evidence oftherapeutic nonequivalence, danger of mechanical substitution of original agents still exists in Russia due to lower price of biosimilars - and lackof legislative acts, regulating registration and circulation of such drugs.In this article we characterize biosimilars in great detail and review major problems of their use, that is: aspects of quality control; disparity withoriginal bio-agents in efficacy and safety; clinical trial requirements, registration procedures and subsequent safety control.

биосимилярыбиотехнологиябиотехнологические препаратыдженерикиинсулинрегуляторные нормы регистрации биосимиляров

biosimilarsbiotechnologybiotechnological agentsgenericsinsulinbiosimilar registration regulations

References1

Walsh G. Biopharmaceutical benchmarks 2006 // Nature Biotechnol. - 2006. - № 24. - Р. 769-776. doi:10.1038/nbt0706-769.

Report medicines in development - Biotechnology // PhRMA. - 2006. http://www.phrma.org/files/Biotech202006.pdf.

McCamish M., Woollett G. Worldwide experience with biosimilar development // MAbs. - № 3 (2). - С. 209-17.

Биотехнология. Принципы и применение. Под ред. И. Хиггинса и др. / Пер. с англ. - М., 1988.

Федеральный закон №61 от 12 апреля 2010 г. «Об обращении лекарственных средств».

The Commission of the European Communities (2003) Commission Directive 2003/63/EC of 25 June 2003 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use // In Official Journal of the European Union. - L159. - Р. 46-94 (http://eur-lex.europa.eu/Lex- UriServ/LexUriServ.do?uri=OJ:L:2003:159:0046:0094:EN:PDF).

The European Parliament and the Council of the European Union (2001) Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use // In Official Journal of the European Union. - L311. - Р. 67-128 (http://eur-lex.europa.eu/LexUriServ/LexUriServ. do?uri=OJ:L:2001:311:0067:0128:EN:PDF).

Buehler G.J., Conner D. The FDA Process for Approving Generic Drugs. FDA Office of Generic Drugs. http://www.connectlive. com/events/ genericdrugs/2006.

Questions and answers on generic medicines. EMEA document. EMEA/393905/2006. London, UK: European Medicines Agency. - 2007. Available from: www.emea.europa.eu/pdfs/human/ pcwp/39390506en.pdf [Last accessed 30 January 2010].

Azevedo V.F. Are we prepared to prescribe biosimilars? // Bras J. Rheumatol. - 2010. - № 50 (3). - Р. 221-224.

Kresse G-B. Biosimilars - Science, status, and strategic perspective // Eur. J. Pharm. Biopharm. - 2009. - № 72 (3). - Р. 479-86.

Kuhlmann M., Covic A. The protein science of biosimilars // Nephrol Dial Transplant. - 2006. - № 21 (Suppl 5). - v4-v8. doi:10.1093/ ndt/gfl474.

Misra A. Are biosimilars really generics? // Expert Opin. Biol. Ther. - 2010. - № 10(4). - Р. 489-494.

Jenkins N., Murphy L., Tyther R. Post-translational modifications of recombinant proteins: significance for biopharmaceuticals // Mol. Biotechnol. - 2008. - № 39. - Р. 113-118.

Kozlowski S., Swann P. Current and future issues in the manufacturing and development of monoclonal antibodies // Adv. Drug Del. Rev. - 2006. - № 58. - Р. 707-722.

Misaizu T, Matsuki S, Strickland TW et al. Role of antennary structure of N-linked sugar chains in renal handling of recombinant human erythropoietin // Blood. - 1995. - № 86. - Р. 4097-4104.

Hepner F., Czasar E., Roitinger E., Lubec G. Mass spectrometrical analysis of recombinant human growth hormone (Genotropin) reveals amino acid substitutions in 2% of the expressed protein // Proteome Sci. - 2005. - № 3. - Р. 1-12.

Walsh G. Therapeutic insulins and their large-scale manufacture // Appl Microbiol Biotechnol. - 2005. - № 67. - Р. 151-159.

Home P. Biosimilar insulins // Diabetes Voice 2011. - № 56 (2). - Р. 41-43.

Schellekens H. Biosimilar therapeutics-what do we need to consider? // NDT Plus. - 2009. - № 2(Suppl 1). - i27-i36. doi: 10.1093/ ndtplus/sfn177.

Kuhlmann M., Marre M. Lessons learned from biosimilar epoetins and insulins // Br J. Diabetes Vasc Dis. - 2010. - № 10. - Р. 90-97.

Roger S.D. and Ashraf M. Biosimilars: Opportunity or Cause for Concern? // J. Pharm. Pharmaceut. Sci. - 2007. - № 10 (3). - Р. 405-410. www. cspsCanada.org.

Casadevall N., Nataf J., Viron B. et al. Pure red-cell aplasia and antieryth¬ropoietin antibodies in patients treated with recombinant erythropoi¬etin // N. Engl. J. Med. - 2002; 346: 469-475.

Sharma B., Bader F., Templeman T. et al. Technical investigations into the cause of the increased incidence of antibody-mediated pure red cell aplasia associated with Eprex // Eur. J. Hospital Pharm. - 2004; 5:86-91.

European Medicines Agency Withdrawal Assessment Report for Insulin Human 30/70 Mix Marvel. - 2008. http://www.ema.europa.eu/ humandocs/PDFs/EPAR/insulinhumanrapidmarvel/701790en.pdf. Accessed 12 May 2010.

European Medicines Agency Withdrawal Assessment Report for Insulin Human Rapid Marvel. - 2007. http://www.ema.europa.eu/humandocs/ PDFs/EPAR/insulinhumanrapidmarvel/31777807en.pdf. Accessed 12 May 2010.

European Medicines Agency Withdrawal Assessment Report for Insulin Human Long Marvel. - 2008. http://www.ema.europa.eu/humandocs/ PDFs/EPAR/insulinhumanrapidmarvel/7034908en.pdf. Accessed 12 May 2010.

Lispi M., Datola A., Bierau H. et al. Heterogeneity of commercial recombinant human growth hormone (r-hGH) preparations containing a thioether variant // Journal of Pharmaceutical Sciences. - 2009; 98(12): 4511-4524. DOI: 10.1002/jps.21774

Singh A.K. Biosimilar epoetins: potential for variation reinforces need for regulation // Nephrology Times. - 2008; 1 (4): P. 2-14.

Schellekens H. Biosimilar epoetins: how similar are they? // Eur. J. Hosp. Pharm. - 2004; 3:8-12.

Raditpornsilpa K., Tiranathanagul K., Kupatawintu P. Et al. Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies // Kidney International. - 2011; 80: P. 88-92; doi:10.1038/ki.2011.68.

US Food and Drug Administration. www.fda.org. Accessed 02 September 2010.

The European Parliament and the Council of the European Union (2004) Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use // In Official Journal of the European Union, L136, pp. 34-57 (http://eur-lex.europa.eu/ LexUriServ/LexUriServ.do?uri=OJ:L:2004:136:0034:0057:EN:PDF).

European Medicines Agency. Guideline on Similar Biological Medicinal Products, CPMP/437/04, October 2005. www.ema.europa.eu/pdfs/ human/biosimilar/043704en Accessed 29 April 2010.

European Medicines Agency. Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Drug Substance - Non Clinical and Clinical Issues, EMEA/CHMP/ BMWP/42832/05, February 2006. www.ema.europa.eu/pdfs/ human/biosimilar/4283205en Accessed 02 September 2010.

European Medicines Agency. Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: Quality Issues, CHMP/49348/05, February 2006. www.ema.europa.eu/pdfs/ human/biosimilar/4934805en Accessed 02 September 2010.

European Medicines Agency. Guideline on Immunogenicity Assessment of Biotechnology-derived Therapeutic Proteins. EMEA/CHMP/ BMWP/14327/2006, December 2007. http://www.ema.europa. eu/docs/en_GB/document_library/Scientific_guideline/2009/09/ WC500003946.pdf. Accessed 02 September 2010.

European Medicines Agency. Annex Guideline on Similar Biological Medicinal Products Containing Biotechnologyderived Proteins as Drug Substance - Non Clinical and Clinical Issues containing Recombinant Human Erythropoietin, CHMP/94526/05, March 2006. www.ema.europa.eu/ pdfs/human/biosimilar/9452605en. Accessed 02 September 2010.

European Medicines Agency. Annex Guideline on Similar Biological Medicinal Products Containing Biotechnology derived Proteins as Drug Substance - Non Clinical and Clinical Issues containing Recombinant Human Growth Hormone, CHMP/94528/05, February 2006. www.ema.europa. eu/pdfs/human/biosimilar/9452805en Accessed 02 September 2010.

European Medicines Agency. Annex Guideline on Similar Biological Medicinal Products Containing Biotechnology derived Proteins as Drug Substance - Non Clinical and Clinical Issues. Guidance on Similar Medicinal Products Containing Recombinant Human Insulin CHMP/ BMWP/32775/05, February 2006. www.ema.europa.eu/pdfs/ human/biosimilar/3277505en. Accessed 02 September 2010.

European Medicines Agency. Annex Guideline on Similar Biological Medicinal Products Containing Biotechnology derived Proteins as Drug Substance -Non Clinical and Clinical Issues containing Recombinant Granulocyte Colony-Stimulating Factor, CHMP/31329/05, February 2006. www.ema.europa.eu/pdfs/human/biosimilar/3132905en Accessed 02 September 2010.

European Medicines Agency. Guideline on Similar Biological Medicinal Products Containing Low-molecular Weight Heparins. Draft released for consultation in April 2008. www.ema.europa.eu/pdfs/human/ biosimilar/11826407en Accessed 02 September 2010.

Юргель Н.В. Система надзора и контроля в сфере обращения лекарственных средств в Российской Федерации // Вестник Росздравнадзора 2008, №6, C. 4-11.

European Generic Medicines Association. Biosimilar medicines: FAQ. Available at: http://198.170.119.137/doc/FAQ_biosimilars.pdf. Accessed 03 May 2010.

The authors declare that there are no conflicts of interest present.