Blood preparations of humans and animals in terms of their quality, efficacy and safety

The problems of quality and safety products derived from human blood plasma and hyperimmune animal sera as well as recombinant blood products resolved strict government regulation of their production processes. The risk of implications is minimized by plasma fractionation and purification of a specific drugs from various impurities (immunoglobulin aggregates, protease, plasmin, plasminogen, prekallikrein activator, IgA and IgM etc.). Viral safety is achieved by multi-step manufacturing process that includes at least two independent methods (treatment with solvent/detergent + incubation at low pH or pasteurization, combined with polyethylene glycol processing). It was justified that for today the technological process of the development of plasma preparations and hyperimmune animal sera has reached its limit. Their further development is the most likely to refer to specific improvements. The improvements will relate to increasing the efficiency of manufacturing technologies and methods of clinical use (preparations for subcutaneous administration, combinations of different immunoglobulin preparations, etc.), viral safety, ways to eliminate component, that were previously not considered to be able to influence the outcome of clinical use (soluble molecules CD4, CD8, HLA, thrombin, trace amounts of blood clotting factors VIII, IX, X, XI, XII etc.). At the same time new genetic engineered preparations with well-characterized molecular composition and a high selectivity for target impact are expected to appear on the market because of these unsolved issues. These are recombinant blood factors with altered properties; cocktails of recombinant antibodies and Fab-fragments of IgG, highly affine for toxin epitopes, etc. Therefore, in the upcoming years it is necessary to create in Russia a new system for assessing the quality, efficacy and safety of blood products, taking into account the future course of their development.

Иммуноглобулины для внутривенного введения, Fc-фрагмент, IgG, поликлональное антитело, мономерные IgG, корь, иммуноглобулины для внутримышечного применения, изоагглютинины к антигенам А, В, D, ВИЧ 1, ВИЧ 2, вирусы гепатитов А, В и С, парвовирус В19, HBsAg, криопреципитат, сепсис, ВОЗ, прион, intravenous immunoglobulin, Fc-fragment, IgG, polyclonal antibody, monomeric IgG, measles, immunoglobulins for intramuscular administration, isoagglutinins to antigens A, B, D, HIV-1, HIV-2, hepatitis A, B and C, parvovirus B19, HBsAg, cryoprecipitate, sepsis, WHO, prion

1. Кольцова К.Л. Использование патентной документации на различных этапах научно-исследовательских и конструкторских разработок. М.; 1984.

2. Александров Л.В., Карпова Н.Н. Методы прогнозирования технических решений с использованием патентной информации. М.; 1991.

3. Донюш Е.К. Использование внутривенных иммуноглобулинов в клинической практике. Вопросы современной педиатрии 2011; (2): 49-63.

4. Radosevich M., Burnouf T. Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance. Vox Sang. 2010; 98(1): 12-28.

5. Галактионов В.Г. Эволюционная иммунология. М.; 2005.

6. Борисевич И.В., Авдеева Ж.И., Алпатова Н.А., Давыдов Д.С., Гайдерова Л.А., Горбунов М.А., с соавт. Медицинские иммунобиологические препараты. М.; 2011.

7. Oncley J.L., Melin M., Richert D.A., Cameron J.W., Gross P.M. The separation of the antibodies, isoagglutinins, prothrombin, plasminogen and beta1-lipoprotein into sub fractions of human plasma. J Am Chem Soc. 1949; 71(2): 541-50.

8. Marcia C., Zago N., Carla L.D. Immunoglobulin: production, mechanisms of action and formulations. Rev Bras Hematol Hemoter. 2011; 33(5): 377-82.

9. Зубкова Н.Б. Биотехнологические аспекты эффективной и безопасной переработки донорской плазмы: проблемы и перспективы. Биопрепараты 2014; ( 1 ): 4-10.

10. Bertolini J. Chromatographic purification of immunoglobulins downstream. Biotechnol Prog. 2000; 31: 20-1.

11. Teschner W., Butterweck H.A., Auer W., Muchitsch E.M., Weber A., Liu S.L., et al. A new liquid, intravenous immunoglobulin product (IGIV 10%) highly purified by a state-of-the-art process. Vox Sang. 2007; 92(1): 42-55.

12. Terpstra F.G., Parkkinen J., Tolo H., Koenderman A.H., Ter Hart H.G., von Bonsdorff L., et al. Viral safety of Nanogam, a new 15 nm-filtered liquid immunoglobulin product. Vox Sang. 2006; 90(1): 21-32.

13. Stucki M., Boschetti N., Schafer W., Hostettler T., Kasermann F., Nowak T., et al. Investigations of prion and virus safety of a new liquid IVIG product. Biologicals 2008; 36(4): 239-47.

14. Burton S.J., Baldes B., Curling J., Haves T.K., Chen D.-N., Bryant C. Sequential protein isolation and purification sсhemes by affinity chromatography. Patent WO № 2006/023831; 2006.

15. Hooper J.A. Intravenous immunoglobulins: evolution of commercial IVIG preparations. Immunol Allergy Clin North Am. 2008; 28(4): 765-78.

16. Углова Т.А. Подкожное введение иммуноглобулина при заместительной терапии у детей с первичными иммунодефицитами. Медицинские новости. 2014; (5):47-51.

17. Jolles S., Stein M. Longhurst H., Borte M., Ritchie B., Sturzenegger M., Berger M. New frontiers in subcutaneous immunoglobulin treatment. Biol Ther. 2011; 1(1): 003. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873072/pdf/13554_2011_Article_9.pdf (cited 2015 July 10).

18. Frost G.I. Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration. Expert Opin Drug Deliv. 2007; 4(4): 427-40.

19. Yap P.L. Intravenous immunoglobulin and hepatitis C virus: an overview of transmission episodes with emphasis on manufacturing data. Clin Ther. 1996; 18(Suppl B): 43-58.

20. Панов В.П. Принципы обеспечения вирусной безопасности продуктов крови. Химико-фармацевтический журн. 2004; 38(3): 39-47.

21. Tsen S., Kingsley D.H., Kibler K., Sizemore S., Sara M., Vaiana P. Pathogen reduction in human plasma using an ultrashort pulsed laser. PLoS/Ohe 2014; 9(11): e111673.

22. Kim S., Yong W.C., Yong K., Hark M.S., Ki W., Yong-Sung K. Improvement of virus safety of an antihemophilc factor IX by virus filtration process. J. Microbiol. Biotechnol. 2008; 18(7): 1317-25.

23. Norrby E. Prions and protein-folding diseases. J Intern Med. 2011; 270(1): 1-14.

24. Покровский В.И., Киселев О.И., Черкасский Б.Л. Прионы и прионные болезни. М.; 2004.

25. Шкундина И.С., Тер-Аванесян М.Д. Прионы. Успехи биол. химии 2006; 46: 3-42.

26. Hilton D.A., Ghani A.C., Conyers L., Edwards P., McCardle L., Ritchie D., et al. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol. 2004; 203(3): 733-9.

27. Gill O.N., Spencer Y., Richard-Loendt A., Kelly C., Dabaghian R., Dabaghian R., et al. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ. 2013; 347: f5675.

28. Legname G., Trian Le N.T., Giachin G. Synthetic prion. In: Prusiner SB. Prions and prion diseases: new developments. 2012; Nova Science Pablishers, Inc. P. 61-83.

29. Llewelyn C.A., Hewitt P.E., Knight R.S., Amar K., Cousens S., Mackenzie J., Will R.G. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004; 363(9407): 417-21.

30. Peden A.H., Head M.W., Ritchie D.L., Bell J.E., Ironside J.W. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004; 364(9433): 527-9.

31. Peden A., McCardle L., Head M.W., Love S., Ward H.J., Cousens S.N., et al. Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. Haemophilia 2010; 16(2): 296-304.

32. Saborio G.P., Permanne B., Soto C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 2001; 411(6839); 810-13.

33. Lacroux C., Comoy E., Moudjou M., Perret-Liaudet A., Lugan S., Litaise C., et al. Preclinical Detection of Variant CJD and BSE Prions in Blood. PLoS Pathog 2014; 10(6): e1004202. Available from: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004202 (cited 2015 July 10).

34. Surround Optical Fiber Immunoassay. Available from: https://en.wikipedia.org/wiki/Surround_Optical_Fiber_Immunoassay (cited 2015 July 10).

35. Rubenstein R., Chang B., Gray P., Piltch M., Bulgin M.S., Sorensen-Melson S., Miller M.W. Prion disease detection, PMCA kinetics, and IgG in urine from sheep naturally/experimentally infected with Scrapie and deer with preclinical/clinical Chronic Wasting Disease. J Virol. 2011; 85(17): 9031-8.

36. Prusiner S.B. Prion protein standard end method of making same. Патент Канады, № 2349337; 2000.

37. Schwartz R. Overview of the biochemistry and safety of a new native intravenous gammaglobulin, IGIV, pH 4.25. Amer J Med. 1987; 83 (4A): 46-52.

38. Абрамова Е.Г., Никифоров А.К., Лобовикова О.А., Еремин С.А., Васин Ю.Г., Михеева Т.А., с соавт. Производство гетерологичного антирабического иммуноглобулина - итоги первых пяти лет. Проблемы особо опасных инфекций 2010; 3(105): 58-62.

39. Ситник Н.П. Разработка высокоочищенного препарата иммуноглобулина антирабического из плазмы крови лошади дис.. канд биол. наук. 2007 Available from: http://www.dissercat.com/content/razrabotka-vysokoochishchennogo-preparata-immunoglobulina-antirabicheskogo-iz-plazmy-krovi-l (cited 2015 July 10).

40. Alvarenga L.M., Zahid M., di Tommaso A., Juste M.O., Aubrey N., Billiald P., Muzard J. Engineering Venom’s Toxin-Neutralizing Antibody Fragments and Its Therapeutic Potential. Toxins. 2014; 6(8): 2541-67.

41. Goyffon M. Passive immunotherapy today: Brief history. Biol Aujourdhui. 2010; 204(1): 51-4.

42. Орлов Б.Н., Гелашвили Д.Б. Зоотоксинология (ядовитые животные и их яды). М.; 1985.

43. Li D., Mattoo P., Keller J.E. New equine antitoxins to botulinum neurotoxins serotypes A and B. Biologicals 2012; 40(4): 240-6.

44. Werdan K., Pilz G., Muller-Werdan U., Enriquez M.M., Schmitt D.V., Mohr F.W., et al. Immune globulin G treatment of post cardiac surgery patients with score-identified severe SIRS - The ESSICS study. Crit Care Med. 2008; 36(3): 716-23.

45. Lou J., Geren I., Garcia-Rodriguez C., Forsyth C.M., Wen W., Knopp K., et al. Affinity maturation of human botulinum neurotoxin antibodies by light chain shuffling via yeast mating. Protein Engineering, Design & Selection 2010; 23(4): 311-9.

46. Burnouf T. Recombinant plasma proteins. Vox Sang. 2011; 100(1): 68-83.

47. Wood W.I., Capon D.J., Simonsen C.C., Eaton D.L., Gitschier J., Keyt B., et al. Expression of active human factor VIII from recombinant DNA clones. Nature 1984; 312(5992): 330-7.

48. Kurachi K., Davie E.W. Isolation and characterization of a cDNA coding for human factor IX. Proc Natl Acad Sci USA. 1982; 79(21): 6461-4.

49. Орлова Н.А., Ковнир С.В., Воробьев И.И., Габибов A.Г., Воробьев А.И. Фактор свертывания крови VIII - от эволюции к терапии. Acta naturae 2013; 5(2): 19-39.

50. Mccue J., Osborne D., Dumont J., Peters R., Mei B., Pierce G.F., et al. Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein. Haemophilia 2014; 20(4): 327-35.

51. Peyvandi F., Garagiola I., Seregni S. Future of coagulation factor replacement therapy. J Thrombosis Haemostasis 2013; 11(Suppl. 1): 84-98.

52. Peters R.T., Low S.C., Kamphaus G.D., Dumont J.A., Amari J.V., Lu Q., et al. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood 2010; 115(10): 2057-64.

53. Food and Drug Administration. CFRCode of Federal Regulations Title 21, Part 58-Good Laboratory Practice. Available from: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=58 (cited 2015 July 10).

54. International Conference on Harmonisation (ICH). International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Viral safety evaluation of biotechnology products derived from cell lines of human or animal origin. Q5A(R1). Available from: http://private.ich.org/LOB/media/MEDIA425.pdf (cited 2015 July 10).

55. Department of Health and Human Services (DHHS). Center for Biologics Evaluation and Research. Points to consider in the characterization of cell lines used to produce biologicals. Available from: http://www.fda.gov/downloads/biologicsbloodvaccines/safetyavailability/ucm162863.pdf. (cited 2015 July 10).