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Generics and the specific features of their regulation

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The article discusses the factors that influence the efficacy and safety of generic drugs, including regular generics, biosimilars, and generic nonbiological complex drugs. It emphasizes the importance of adequate regulatory requirements to provide a comparable therapeutic efficacy and a comparable cost-effectiveness ratio for generics versus brand-name drugs.

About the Authors

E. A. Ushkalova
Department of General and Clinical Pharmacology, Peoples' Friendship University of Russia, Moscow, Russia 6, Miklukho-Maklai St., Moscow 117198
Russian Federation

S. K. Zyryanov
Department of General and Clinical Pharmacology, Peoples' Friendship University of Russia, Moscow, Russia 6, Miklukho-Maklai St., Moscow 117198
Russian Federation

A. V. Ushkalova
Mental Health Clinic, Moscow Region, Russia 120 Zhivopisnaya St., Village of Lenino, Istrinsky District, Moscow Region 143590
Russian Federation


1. Herxheimer A. Independent drug bulletins: answers to pressing questions. Монитор основных лекарств. 1995;(3):19. [Herxheimer A. Nezavisimye lekarstvennye byulleteni: otvety na nasushchnye voprosy. Monitor osnovnykh lekarstv. 1995;(3):19. (In Russ.)].

2. Videau JV, Fundafunda B. Generic drugs: the hidden issues of quality and cost. WHO Drug Information. 2000;77-81.

3. WorldHealth Organization, 1996, WHO Expert Expert Committee on Specifications for Pharmaceutical Preparations: thirty-fourth report. WHO Technical Report Series No. 863. Geneva. P. 114-54.

4. ФЗ №61 «Об обращении ЛС» от 12 апреля 2010 г. (с изменениями и дополнениями). [Federal law N61 «On circulation of drugs» dated 12 April 2010 (with amendments and additions). (In Russ.)].

5. Белоусов ЮБ, Зырянов СК. Дженерики или бренды: pro et contra. Качественная клиническая практика. 2003;(2):95-100. [Belousov YuB, Zyryanov SK. Generics or brands: pro et contra. Kachestvennaya klinicheskaya praktika. 2003;(2):95-100. (In Russ.)].

6. Genazzani AA, Pattarino F. Difficulties in the production of identical drug products from a pharmaceutical technology viewpoint. Drugs R D. 2008;9(2):65-72.

7. Shete G, Puri V, Kumar L, Bansal AK. Solid state characterization of commercial crystalline and amorphous atorvastatin calcium samples. AAPS PharmSciTech. 2010 Jun;11(2): 598- 609. doi:10.1208/s12249-010-9419-7. Epub 2010 Mar 30.

8. Пушкарь ДЮ, Берников АН, Дьяков ВВ. Проскар или генерики: комментарий клинициста. Фарматека. 2007;(4):63–6. [Pushkar' DYu, Bernikov AN, D'yakov VV. Proscar or generic: comments of clinician. Farmateka. 2007;(4):63–6. (In Russ.)].

9. Taylor PW, Keenan MH. Pharmaceutical quality of generic isotretinoin products, compared with Roaccutane. Curr Med Res Opin. 2006 Mar;22(3):603-15.

10. Kucharz EJ, Kovalenko V, Szanto S, et al. A review of glucosamine for knee osteoarthritis: why patented crystalline glucosamine sulfate should be differentiated from other glucosamines to maximize clinical outcomes. Curr Med Res Opin. 2016 Jun;32(6):997- 1004.

11. Silverstein I, Falk A, Carter D, et al. Excipient-Control Strategies. Pharmaceutical Technology. Volume 2008 Supplement, Issue 5. controlstrategies.

12. Andermann F, Duh MS, Gosselin A, et al. Adverse clinical consequences of compulsory generic switching of antiepileptic drugs. Program and abstracts of the First North American Regional Epilepsy Congress: 60th Annual Meeting of the American Epilepsy Society; December 1-5, 2006; San Diego, California. Abstract 2.206.

13. Rascati KL, Richards KM, Johnsrud MT, Mann TA. Effects of antiepileptic drug substitutions on epileptic events requiring acute care. Pharmacotherapy. 2009 Jul;29(7):769-74.

14. Berg MJ, Gross RA. Physician and patients perceive that generic drug substi-tution of antiepileptic drugs can cause breakthrough seizuresresults from a US survey. Program and abstracts of the First North American Regional Epilepsy Congress: 60th Annual Meeting of the American Epilepsy Society; December 1–5, 2006; San Diego, California. Abstract 2.105.

15. Jonathan D Quick; Management Sciences for Health (Firm); Action Programme on Essential Drugs and Vaccines (World Health Organization). Managing Drug Supply. Kumarian Press. West Hartford, Conn., USA : Kumarian Press, 1997.

16. Argumosa A, Herranz JL. The clinical and economic impact of generic drugs in the treatment of epilepsy. Rev Neurol. 2005 Jul 1-15; 41(1):45-9.

17. Gothe H, Schall I, Saverno K, et al. The Impact of Generic Substitution on Health and Economic Outcomes: A Systematic Review. Appl Health Econ Health Policy. 2015 Aug;13 Suppl 1:S21-33.

18. Ramos AS, Schmidt CA, Andrade SS, et al. Biological evaluation of recombinant human rythropoietin in pharmaceutical products. Braz J Med Biol Res. 2003 Nov;36(11):1561-9. Epub 2003 Oct 22.

19. Goncalves J, Araujo F, Cutolo M, Fonseca JE. Biosimilar monoclonal antibodies: preclinical and clinical development aspects. Clin Exp Rheumatol. 2016 Jul-Aug;34(4): 698- 705. Epub 2016 Jul 4.

20. Солдатов АА, Авдеева ЖИ, Алпатова НА и др. Фармакокинетические свойства препаратов белковой природы. Биопрепараты. 2015;(2):24-35. [Soldatov AA, Avdeeva ZhI, Alpatova N, et al. The pharmacokinetic properties of the protein drugs. Biopreparaty. 2015;(2): 24-35. (In Russ.)].

21. Gershon SK, Luksenburg H, Cote TR, Braun MM. Pure red-cell aplasia and recombinant erythropoietin. N Engl J Med. 2002 May 16;346(20):1584-6; author reply 1584-6.

22. Liu L. Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins. J Pharm Sci. 2015 Jun;104(6):1866-84.

23. Brady LJ, Velayudhan J, Visone DB, et al. The criticality of high-resolution N-linked carbohydrate assays and detailed characterization of antibody effector function in the context of biosimilar development. MAbs. 2015;7(3):562-70.

24. Jefferis R. Posttranslational Modifications and the Immunogenicity of Biotherapeutics. J Immunol Res. 2016;2016:5358272. doi:10.1155/2016/5358272. Epub 2016 Apr 14.

25. Schelleken H. Factors influencing the immunogenicity of therapeutic proteins. Nephrol Dial Transplant. 2005 Jun;20 Suppl 6:vi3-9.

26. Camacho LH, Frost CP, Abella E, et al. Biosimilars 101: considerations for U.S. oncologists in clinical practice. Cancer Med. 2014;3(4):889-99.

27. Eleryan MG, Akhiyat S, Rengifo-Pardo M, Ehrlich A. Biosimilars: potential implications for clinicians. Clin Cosmet Investig Dermatol. 2016 Jun 17;9:135-42. doi:10.2147/CCID.S91691. eCollection 2016.

28. Tovey MG, Lallemand C. Immunogenicity and other problems associated with the use of biopharmaceuticals. Ther Adv Drug Saf. 2011 Jun;2(3):113-28.

29. Rudick RA, Goelz SE. Beta-interferon for multiple sclerosis. Exp Cell Res. 2011 May 15; 317(9):1301-11.

30. Schellekens H. Biosimilar therapeutics-what do we need to consider? NDT Plus. 2009;2(Supplement 1):i27-i36.

31. World Health Organization Programme on International Non-Proprietary Names (INN), Quality Assurance and Safety: Medicines (QSM), and Essential Medicines and Health Products (EMP) Executive Summary: Proceedings of the 55th Consultation on International Nonproprietary Names for Pharmaceutical Substances; Geneva; 2012. Oct 16-18

32. Daller J. Biosimilars: a consideration of the regulations in the United States and European union. Regul Toxicol Pharmacol. 2016 Apr;76: 199-208. doi:10.1016/j.yrtph.2015.12.013. Epub 2015 Dec 28.

33. AIMP: в России зарегистрировано более 40 биоаналогов.

34. McCamish M, Woollett G. Worldwide experience with biosimilar development. MAbs. 2011 Mar–Apr;3(2):209-17. Epub 2011 Mar 1.

35. Lean QY, Patel RP, Stewart N, et al. Identification of pro- and anti-proliferative oligosaccharides of heparins. Integr Biol (Camb). 2014 Jan;6(1):90-9.

36. Crommelin DJ, Shah VP, Klebovich I, et al. The similarity question for biologicals and nonbiological complex drugs. Eur J Pharm Sci. 2015 Aug 30;76:10-7. doi:10.1016/j.ejps.2015.04.010. Epub 2015 Apr 23.

37. Schellekens H, Stegemann S, Weinstein V, et al. How to regulate nonbiological complex drugs (NBCD) and their follow-on versions: points to consider. AAPS J. 2014 Jan;16(1):15-21.

38. Шварц ГЯ, Раменская ГВ. Анализ причин практической невозможности создания генериков копаксона. Химико-фармацевтический журнал. 2012;46(11):29-34. [Shvarts GYa, Ramenskaya GV. Analysis of the reasons for the practical impossibility of creating generics of Copaxone. Khimiko-farmatsevticheskii zhurnal. 2012;46(11):29-34. (In Russ.)].

39. Шварц ГЯ, Раменская ГВ. Некоторые вопросы регулирования обращения небиологических лекарственных средств сложного химического строения. Химико- фармацевтический журнал. 2015;49(4):3-10. [Shvarts GYa, Ramenskaya GV. Some issues of regulation of non-biological medicines with complex chemical structure. Khimiko- farmatsevticheskii zhurnal. 2015;49(4):3-10. (In Russ.)].

40. Jalilian B, Einarsson HB, Vorup-Jensen T. Glatiramer acetate in treatment of multiple sclerosis: a toolbox of random co-polymers or targeting inflammatory mechanisms of both the innate and adaptive immune system? Int J Mol Sci. 2012 Nov 9;13(11):14579-605. doi:10.3390/ijms131114579.

41. Duncan R, Gaspar R. Nanomedicine(s) under the microscope. Mol Pharm. 2011 Dec 5;8(6):2101-41. doi:10.1021/mp200394t. Epub 2011 Oct 26.

42. GaBI Online – Generics and Biosimilars Initiative. EU guidelines for biosimilars. Mol, Belgium: Pro Pharma Communications International guidelines-for-biosimilars.

43. Bakshi S, Chalifa-Caspi V, Plaschkes I, et al. Gene expression analysis reveals functional pathways of glatiramer acetate activation. Expert Opin Ther Targets. 2013 Apr;17(4):351- 62.

44. European Medicines Agency. Guideline on clinical investigation of medicinal products for the treatment of multiple sclerosis. CPMP/EWP/561/98 Rev 1. 16 November 2006

45. Nicholas J. Clinical development, immunogenicity, and interchangeability of follow-on complex drugs. Generics and biosimilar initiatives journal. 5/08/2014. http://gabi-

46. Ruiz SJL, Lopez-Ruiz M, Barroso-Rodriguez N, et al. Safety and pharmacodynamics comparative study to evaluate the effect of glatiramer acetate (Probioglat® and Copaxone®) study drug and reference drug on Th1, Th2 and sVCAM response in patients with relapsing-remitting multiple sclerosis. Rev Mex Neuroci. 2013;(14):306-13.

47. Conner J. Glatiramer acetate and therapeutic peptide vaccines for multiple sclerosis. J Autoimmun Cell Resp. 2014;(1):3.

48. Cohen J, Belova A, Selmaj K. Equivalence of generic glatiramer acetate in multiple sclerosis: a randomized clinical trial. JAMA Neurol. 2015 Dec;72(12):1433-41.

49. Ramirez D, Flores J, Verdi D, et al. Rates of adverse events and multiple sclerosis relapses before and after introduction of a purported generic glatiramer acetate in Mexico: results from a large patient support program in Mexico. Value Health. 2015 Nov;18(7):A877.

50. Sorensen PS. Multiple sclerosis. Generic glatiramer acetate – a step toward cheaper MS drugs? Nat Rev Neurol. 2016 Jan;12(1):5-6.

For citation:

Ushkalova E.A., Zyryanov S.K., Ushkalova A.V. Generics and the specific features of their regulation. Neurology, Neuropsychiatry, Psychosomatics. 2016;8(3):82-87. (In Russ.)

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