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DOI: 10.1055/a-1894-1146
Hyperimmunplasma: Gewinnung, Verarbeitung und therapeutische Anwendungen
Hyperimmune Plasma: Collection, Processing and Therapeutic Applications![](https://www.thieme-connect.de/media/transfusionsmedizin/202301/lookinside/thumbnails/18941146_10-1055-a-1894-1146-1.jpg)
Zusammenfassung
Das Prinzip der passiven Immunisierung ist seit dem 19. Jahrhundert bekannt und wird auch bei aktuellen Pandemien als Ansatz zur Prophylaxe und Therapie eingesetzt. Der Schutz wird hierbei übertragen durch Blut, Serum oder Plasma, welche Immunglobuline gegen spezifische Krankheitserreger, Bakterientoxine oder sonstige Antigene enthalten, sowie durch aus Humanplasma industriell aufgereinigte Immunglobuline. Die aktuell verwendeten Reinigungsverfahren für Immunglobuline aus Humanplasma beruhen auf der von Edwin J. Cohn entwickelten Fraktionierung von Plasma. Zur Gewinnung von Immunglobulinen mit hohen Antikörpertitern gegen spezifische Antigene, sogenannte Hyperimmunglobuline, muss zunächst Hyperimmunplasma gezielt von ausgewählten Spendern gewonnen werden. Diese Spender haben erhöhte Antikörpertiter gegen spezifische Krankheitserreger, Bakterientoxine oder sonstige Antigene, wenn sie im Rahmen einer vorangegangenen Infektion natürlich immunisiert wurden, einen zugelassenen Impfstoff zur Immunisierung erhalten haben oder gezielt zum Zweck der Plasmaspende immunisiert wurden. Aktuell sind in Deutschland, Österreich und der Schweiz Hyperimmunglobulinprodukte für verschiedene Anwendungen im Patienten zugelassen, von denen die meisten aus humanem Blutplasma gewonnen werden. Um die Herstellung der Produkte und damit letztlich die Behandlung der Patienten gewährleisten zu können, werden resiliente Lieferketten benötigt. Hierzu bedarf es unter anderem Änderungen in den Rahmenbedingungen für die Spenderimmunisierung in Deutschland.
Abstract
The concept of passive immunization has been known since the 19th century and is also used in current pandemics as an approach to prophylaxis and therapy. Protection is conferred by blood, serum or plasma containing immunoglobulins against specific pathogens, bacterial toxins or other antigens, as well as by immunoglobulins industrially purified from human plasma. The currently used purification methods for immunoglobulins from human plasma are based on the fractionation of plasma developed by Edwin J. Cohn. To obtain immunoglobulins with high antibody titers to specific antigens, so-called hyperimmunoglobulins, hyperimmune plasma must first be obtained from selected donors. These donors have elevated antibody titers against specific pathogens, bacterial toxins or other antigens if they have been naturally immunized as part of a previous infection, have received an approved vaccine for immunization or have been specifically immunized for the purpose of plasma donation. Currently, hyperimmunoglobulin products are approved in Germany, Austria and Switzerland for various applications in patients, most of which are derived from human blood plasma. Resilient supply chains are needed to ensure the manufacture of the products and ultimately the treatment of patients. This requires, among other things, changes in the framework for donor immunization in Germany.
Publication History
Article published online:
21 February 2023
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Literatur
- 1 Tharmalingam T, Han X, Wozniak A. et al. Polyclonal hyper immunoglobulin: A proven treatment and prophylaxis platform for passive immunization to address existing and emerging diseases. Human vaccines & immunotherapeutics 2022; 18: 1886560 DOI: 10.1080/21645515.2021.1886560.
- 2 Sparrow E, Friede M, Sheikh M. et al. Therapeutic antibodies for infectious diseases. Bulletin of the World Health Organization 2017; 95: 235-237 DOI: 10.2471/blt.16.178061.
- 3 World Health Organization. World Health Organization model list of essential medicines: 21st list 2019 (WHO/MVP/EMP/IAU/2019.06) (Licence: CC BY-NC-SA 3.0 IGO) Im Internet: https://apps.who.int/iris/handle/10665/325771; Stand: 01.11.2022
- 4 Pelletier JPR, Mukhtar F. Passive Monoclonal and Polyclonal Antibody Therapies. Immunologic Concepts in Transfusion Medicine 2020; DOI: 10.1016/b978-0-323-67509-3.00016-0:.
- 5 Cagdas D. Convalescent plasma and hyperimmune globulin therapy in COVID-19. Expert review of clinical immunology 2021; 17: 309-316 DOI: 10.1080/1744666x.2021.1894927.
- 6 Deutscher Bundestag. Verunreinigungen von Arzneimitteln mit Valsartan (Drucksache 19/4073) (29.08.2018). Im Internet: https://dserver.bundestag.de/btd/19/040/1904073.pdf; Stand: 31.10.2022
- 7 Gustafson M. The Role of Hyperimmune Plasma Im Internet: https://www.pptaglobal.org/images/source/2019/Fall/5._The_Role_of_Hyperimmune_Plasma.pdf; Stand: 09.11.2022
- 8 ITAC (INSIGHT 013) Study Group. Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial. Lancet (London, England) 2022; 399: 530-540 DOI: 10.1016/s0140-6736(22)00101-5.
- 9 Hansda A, Biswas D, Bhatta A. et al. Plasma therapy: a passive resistance against the deadliest. Human vaccines & immunotherapeutics 2022; 18: 2006026 DOI: 10.1080/21645515.2021.2006026.
- 10 Enke U. 125 Jahre Diphtherieheilserum: „Das Behring’sche Gold“. Dtsch Arztebl 2015; 112: 49 A-2088 / B-1722 / C-1667. 2015
- 11 Behring Ev, und Shibasaburo Kitasato Ueber Das Zustandekommen Der Diphtherie-Immunität Und Der Tetanus-Immunität Bei Thieren. Philipps-Universität Marburg 1890; DOI: 10.17192/eb2013.0164..
- 12 Garraud O, Heshmati F, Pozzetto B. et al. Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow. Transfusion clinique et biologique: journal de la Societe francaise de transfusion sanguine 2016; 23: 39-44 DOI: 10.1016/j.tracli.2015.12.003.
- 13 Marson P, Cozza A, De Silvestro G. The true historical origin of convalescent plasma therapy. Transfusion and apheresis science: official journal of the World Apheresis Association: official journal of the European Society for Haemapheresis 2020; 59: 102847 DOI: 10.1016/j.transci.2020.102847.
- 14 Luke TC, Kilbane EM, Jackson JL. et al. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment?. Annals of internal medicine 2006; 145: 599-609 DOI: 10.7326/0003-4819-145-8-200610170-00139.
- 15 Gulland A. First Ebola treatment is approved by WHO. BMJ (Clinical research ed) 2014; 349: g5539 DOI: 10.1136/bmj.g5539.
- 16 Körper S, Grüner B, Zickler D. et al. One-year follow-up of the CAPSID randomized trial for high-dose convalescent plasma in severe COVID-19 patients. The Journal of clinical investigation 2022; DOI: 10.1172/jci163657..
- 17 Körper S, Weiss M, Zickler D. et al. Results of the CAPSID randomized trial for high-dose convalescent plasma in patients with severe COVID-19. The Journal of clinical investigation 2021; 131 DOI: 10.1172/jci152264.
- 18 Yang P, Wang J, Zheng R. et al. Convalescent plasma may not be an effective treatment for severe and critically ill covid-19 patients: A Systematic Review & Meta-Analysis of Randomized Controlled Trials. Heart & lung: the journal of critical care 2022; 53: 51-60 DOI: 10.1016/j.hrtlng.2022.01.019.
- 19 Thompson MA, Henderson JP, Shah PK. et al. Association of Convalescent Plasma Therapy With Survival in Patients With Hematologic Cancers and COVID-19. JAMA oncology 2021; 7: 1167-1175 DOI: 10.1001/jamaoncol.2021.1799.
- 20 Sullivan DJ, Gebo KA, Shoham S. et al. Early Outpatient Treatment for Covid-19 with Convalescent Plasma. The New England journal of medicine 2022; 386: 1700-1711 DOI: 10.1056/NEJMoa2119657.
- 21 Schroeder HW, Cavacini L. Structure and function of immunoglobulins. The Journal of allergy and clinical immunology 2010; 125: S41-S52 DOI: 10.1016/j.jaci.2009.09.046.
- 22 Bundesärztekammer. Richtlinie zur Gewinnung von Blut und Blutbestandteilen und zur Anwendung von Blutprodukten (Richtlinie Hämotherapie) (2021). Im Internet: https://www.bundesaerztekammer.de/fileadmin/user_upload/_old-files/downloads/pdf-Ordner/RL/RiliH_Lese.pdf; Stand: 25.10.2022
- 23 Council of Europe. European Pharmacopoia Monograph 0853 Human plasma for fractionation. Im Internet: https://pheur.edqm.eu/home
- 24 Council of Europe. European Pharmacopoia Monograph 0557 Human anti-D immunoglobulin. Im Internet: https://pheur.edqm.eu/home
- 25 European Medicines Agency. Guideline on plasma-derived medicinal products (EMA/CHMP/BWP/706271/2010) (07.2011). Im Internet: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-plasma-derived-medicinal-products_en.pdf; Stand: 25.10.2022
- 26 World Health Organization. Requirements for the collection, processing and quality control of blood, blood components and plasma derivatives (TRS No 840). Im Internet: https://cdn.who.int/media/docs/default-source/biologicals/blood-products/who-trs-840-annex2-bts-requirements.pdf?sfvrsn=7afda4c2_2&download=true; Stand: 04.11.2022
- 27 Robert Koch Institut. Hyperimmunplasma (Plasma für besondere Zwecke) zur Herstellung von Hyperimmunglobulinen (speziellen Immunglobulinen) (01.12.1995). Im Internet: https://www.rki.de/DE/Content/Kommissionen/AK_Blut/Voten/Uebersicht/V_11/V11_Hyperimmunplasma.html; Stand: 04.11.2022
- 28 European Agency for the Evaluation of Medicinal Products. Note for guidance on virus validation studies: the design, contribution and interpretation of studies validating the inactivation and removal of viruses (CPMP/BWP/268/95) (1996). Im Internet: https://www.ema.europa.eu/en/documents/scientific-guideline/note-guidance-virus-validation-studies-design-contribution-interpretation-studies-validating_en.pdf; Stand: 04.11.2022
- 29 European Medicines Agency. Guideline on the warning on transmissible agents in summary of product characteristics (SmPCs) and package leaflets for plasma-derived medicinal products (EMA/CHMP/BWP/360642/2010 rev. 1) (2011). Im Internet: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-warning-transmissible-agents-summary-product-characteristics-smpcs-package-leaflets-plasma_en.pdf; Stand: 04.11.2022
- 30 European Medicines Agency. CHMP position statement on Creutzfeldt-Jakob disease and plasma-derived and urine-derived medicinal products (EMA/CHMP/BWP/303353/2010 Rev 3) (2018). Im Internet: https://www.ema.europa.eu/en/documents/scientific-guideline/chmp-position-statement-creutzfeldt-jakob-disease-plasma-derived-urine-derived-medicinal-products_en-0.pdf; Stand: 04.11.2022
- 31 Etscheid M, Breitner-Ruddock S, Gross S. et al. Identification of kallikrein and FXIa as impurities in therapeutic immunoglobulins: implications for the safety and control of intravenous blood products. Vox sanguinis 2012; 102: 40-46 DOI: 10.1111/j.1423-0410.2011.01502.x.
- 32 Ovanesov MV, Menis MD, Scott DE. et al. Association of immune globulin intravenous and thromboembolic adverse events. American journal of hematology 2017; 92: E44-e45 DOI: 10.1002/ajh.24644.
- 33 Deml L, Hüber CM, Barabas S. et al. Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens. Transplantation direct 2021; 7: e781 DOI: 10.1097/txd.0000000000001236.
- 34 CSL Behring. deutsche Fachinformation Tetagam P (04.2022). Im Internet: https://www.fachinfo.de/suche/fi/005365; Stand: 26.10.2022
- 35 Fooks AR, Cliquet F, Finke S. et al. Rabies. Nature reviews Disease primers 2017; 3: 17091 DOI: 10.1038/nrdp.2017.91.
- 36 Robert Koch Institut. Tollwut – RKI-Ratgeber (29.09.2022). Im Internet: https://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Tollwut.html; Stand: 14.10.2022
- 37 CSL Behring. deutsche Fachinformation Berirab (04.2022). Im Internet: https://www.fachinfo.de/suche/fi/005366; Stand: 26.10.2022
- 38 GBD 2019 Hepatitis B Collaborators. Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. The lancet Gastroenterology & hepatology 2022; 7: 796-829 DOI: 10.1016/s2468-1253(22)00124-8.
- 39 Biotest. deutsche Fachinformation Hepatect CP (05.2022). Im Internet: https://www.fachinfo.de/suche/fi/003455; Stand: 25.10.2022
- 40 Kedrion. deutsche Fachinformation VENBIG (02.2022). Im Internet: https://www.fachinfo.de/suche/fi/013561; Stand: 26.10.2022
- 41 CSL Behring. deutsche Fachinformation Hepatitis-B-Immunglobulin Behring (04.2022). Im Internet: https://www.fachinfo.de/suche/fi/001025; Stand: 10.11.2022
- 42 Kedrion. deutsche Fachinformation UMAN BIG (02.2022). Im Internet: https://www.fachinfo.de/suche/fi/013560; Stand: 10.11.2022
- 43 Biotest. deutsche Fachinformation Zutectra (03.2022). Im Internet: https://www.fachinfo.de/suche/fi/012168; Stand: 26.10.2022
- 44 Cornberg M, Sandmann L, Protzer U. et al. S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion – (AWMF-Register-Nr. 021-11). Zeitschrift fur Gastroenterologie 2021; 59: 691-776 DOI: 10.1055/a-1498-2512.
- 45 Lai Q, Mennini G, Giovanardi F. et al. Immunoglobulin, nucleos(t)ide analogues and hepatitis B virus recurrence after liver transplant: A meta-analysis. European journal of clinical investigation 2021; 51: e13575 DOI: 10.1111/eci.13575.
- 46 Cholongitas E, Papatheodoridis GV. High genetic barrier nucleos(t)ide analogue(s) for prophylaxis from hepatitis B virus recurrence after liver transplantation: a systematic review. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2013; 13: 353-362 DOI: 10.1111/j.1600-6143.2012.04315.x.
- 47 European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. Journal of hepatology 2017; 67: 370-398 DOI: 10.1016/j.jhep.2017.03.021.
- 48 Biotest. deutsche Fachinformation Varitect CP (05.2022). Im Internet: https://www.fachinfo.de/suche/fi/002181; Stand: 26.10.2022
- 49 Robert Koch Institut. Windpocken (Varizellen), Gürtelrose (Herpes zoster) – RKI-Ratgeber (01.08.2017). Im Internet: https://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Varizellen.html; Stand: 14.10.2022
- 50 Patil A, Goldust M, Wollina U. Herpes zoster: A Review of Clinical Manifestations and Management. Viruses 2022; 14 DOI: 10.3390/v14020192.
- 51 Kennedy PGE, Gershon AA. Clinical Features of Varicella-Zoster Virus Infection. Viruses 2018; 10 DOI: 10.3390/v10110609.
- 52 Lachmann R, Loenenbach A, Waterboer T. et al. Cytomegalovirus (CMV) seroprevalence in the adult population of Germany. PloS one 2018; 13: e0200267 DOI: 10.1371/journal.pone.0200267.
- 53 Adland E, Klenerman P, Goulder P. et al. Ongoing burden of disease and mortality from HIV/CMV coinfection in Africa in the antiretroviral therapy era. Frontiers in microbiology 2015; 6: 1016 DOI: 10.3389/fmicb.2015.01016.
- 54 Kotton CN, Kumar D, Caliendo AM. et al. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation 2018; 102: 900-931 DOI: 10.1097/tp.0000000000002191.
- 55 Kagan KO, Hamprecht K. Cytomegalovirus infection in pregnancy. Archives of gynecology and obstetrics 2017; 296: 15-26 DOI: 10.1007/s00404-017-4380-2.
- 56 Biotest. deutsche Fachinformation Cytotect CP Biotest (05.2022). Im Internet: https://www.fachinfo.de/suche/fi/004021; Stand: 26.10.2022
- 57 Legler TJ. RhIg for the prevention Rh immunization and IVIg for the treatment of affected neonates. Transfusion and apheresis science: official journal of the World Apheresis Association: official journal of the European Society for Haemapheresis 2020; 59: 102950 DOI: 10.1016/j.transci.2020.102950.
- 58 Gemeinsamer Bundesausschuss. Abschlussbericht: Mutterschafts-Richtlinien: Nicht-invasive Pränataldiagnostik zur Bestimmung des fetalen Rhesusfaktors im Rahmen der MutterschaftsRichtlinie (24.11.2020). Im Internet: https://www.g-ba.de/downloads/40-268-6810/2020-08-20_Mu-RL_Bestimmung-Rhesusfaktor-fetal_ZD.pdf; Stand: 04.11.2022
- 59 Genzyme Europe. deutsche Fachinformation Thymoglobuline (06.2020). Im Internet: https://www.fachinfo.de/suche/fi/006337; Stand: 26.10.2022
- 60 Neovii. deutsche Fachinformation Grafalon (02.2022). Im Internet: https://www.fachinfo.de/suche/fi/013056; Stand: 04.11.2022
- 61 Pfizer. deutsche Fachinformation Atgam (01.2022). Im Internet: https://www.fachinfo.de/suche/fi/023641; Stand: 26.10.2022
- 62 Bundesamt für Sicherheit im Gesundheitswesen. Arzneispezialitätenregister Im Internet: https://aspregister.basg.gv.at/aspregister/faces/aspregister.jspx;jsessionid=BVtBtiV01T94AodbdgGfH5dMGJXBsoxnunFrXWzGbA_u5sSv3DgF!1015778284; Stand: 10.11.2022
- 63 Bundesministerium für Gesundheit. Arzneimittel-Informationssystem. Im Internet: https://www.pharmnet-bund.de/dynamic/de/arzneimittel-informationssystem/index.html; Stand: 10.11.2022
- 64 Refdata. Arzneimittelinformation. Im Internet: https://www.swissmedicinfo.ch/; Stand: 10.11.2022
- 65 White J, Tunga P, Anderson DM. et al. Results of a Double-Blind, Randomized, Placebo-Controlled Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Anti-Zika Virus Immunoglobulin. The American journal of tropical medicine and hygiene 2021; 105: 1552-1562 DOI: 10.4269/ajtmh.20-1578.
- 66 Emond RT, Evans B, Bowen ET. et al. A case of Ebola virus infection. British medical journal 1977; 2: 541-544 DOI: 10.1136/bmj.2.6086.541.
- 67 Mupapa K, Massamba M, Kibadi K. et al. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee. The Journal of infectious diseases 1999; 179: S18-S23 DOI: 10.1086/514298.
- 68 World Health Organization. Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks: interim guidance for national health authorities and blood transfusion services, Version 1.0 (WHO/HIS/SDS/2014.8) Im Internet: https://apps.who.int/iris/handle/10665/135591; Stand: 10.11.2022
- 69 World Health Organization. Position Paper on Collection and Use of Convalescent Plasma or Serum as an Element in Filovirus Outbreak Response (2014). Im Internet: https://www.who.int/publications/m/item/BRN_PositionPaperConvPlasmaFiloviruses; Stand: 10.11.2022
- 70 Ciencewicki JM, Herbert AS, Storm N. et al. Characterization of an Anti-Ebola Virus Hyperimmune Globulin Derived From Convalescent Plasma. The Journal of infectious diseases 2022; 225: 733-740 DOI: 10.1093/infdis/jiab432.
- 71 Huygens S, Hofsink Q, Nijhof IS. et al. Hyperimmune globulin for severely immunocompromised patients hospitalized with COVID-19: a randomized, controlled trial. The Journal of infectious diseases. 2022 DOI: 10.1093/infdis/jiac334.
- 72 Farcet MR, Karbiener M, Knotzer S. et al. Omicron Severe Acute Respiratory Syndrome Coronavirus 2 Neutralization by Immunoglobulin Preparations Manufactured From Plasma Collected in the United States and Europe. The Journal of infectious diseases 2022; 226: 1396-1400 DOI: 10.1093/infdis/jiac358.
- 73 Awasthi M, Golding H, Khurana S. SARS-CoV-2 hyperimmune intravenous human immunoglobulins neutralizes Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.3 and BA.4/BA.5 for treatment of COVID-19. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2022; DOI: 10.1093/cid/ciac642. DOI:10.1093/cid/ciac642
- 74 Remuzzi G, Schiaffino S, Santoro MG. et al. Drugs for the prevention and treatment of COVID-19 and its complications: An update on what we learned in the past 2 years. Frontiers in pharmacology 2022; 13: 987816 DOI: 10.3389/fphar.2022.987816.
- 75 Tzou PL, Tao K, Pond SLK. et al. Coronavirus Resistance Database (CoV-RDB): SARS-CoV-2 susceptibility to monoclonal antibodies, convalescent plasma, and plasma from vaccinated persons. PloS one 2022; 17: e0261045 DOI: 10.1371/journal.pone.0261045.
- 76 Nigro G, Adler SP, La Torre R. et al. Passive immunization during pregnancy for congenital cytomegalovirus infection. The New England journal of medicine 2005; 353: 1350-1362 DOI: 10.1056/NEJMoa043337.
- 77 Revello MG, Lazzarotto T, Guerra B. et al. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. The New England journal of medicine 2014; 370: 1316-1326 DOI: 10.1056/NEJMoa1310214.
- 78 Kagan KO, Enders M, Hoopmann M. et al. Outcome of pregnancies with recent primary cytomegalovirus infection in first trimester treated with hyperimmunoglobulin: observational study. Ultrasound in obstetrics & gynecology: the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 2021; 57: 560-567 DOI: 10.1002/uog.23596.
- 79 Biotest. Prevention of Maternal-fetal Cytomegalovirus Transmission After Primary Maternal Infection, GW ≤ 14 (PreCyssion) (27.12.2021). Im Internet: https://clinicaltrials.gov/ct2/show/NCT05170269; Stand: 25.10.2022
- 80 Rawlinson WD, Hamilton ST, van Zuylen WJ. Update on treatment of cytomegalovirus infection in pregnancy and of the newborn with congenital cytomegalovirus. Current opinion in infectious diseases 2016; 29: 615-624 DOI: 10.1097/qco.0000000000000317.
- 81 Burnouf T, Faber JC, Radosevic M. et al. Plasma fractionation in countries with limited infrastructure and low-/medium income: How to move forward?. Transfusion and apheresis science: official journal of the World Apheresis Association: official journal of the European Society for Haemapheresis 2020; 59: 102715 DOI: 10.1016/j.transci.2019.102715.
- 82 Kurtović T, Ravlić S, Štimac A. et al. Efficient and Sustainable Platform for Preparation of a High-Quality Immunoglobulin G as an Urgent Treatment Option During Emerging Virus Outbreaks. Frontiers in immunology 2022; 13: 889736 DOI: 10.3389/fimmu.2022.889736.
- 83 Lihme A, Hansen MB, Andersen IV. et al. A novel core fractionation process of human plasma by expanded bed adsorption chromatography. Analytical biochemistry 2010; 399: 102-109 DOI: 10.1016/j.ab.2009.12.002.
- 84 Health and Human Services Department and the Food and Drug Administration. Code of Federal Regulations – Title 21 §640.65 Plasmapheresis (b)(8) (11.09.2022). Im Internet: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-F/part-640/subpart-G/section-640.65; Stand: 04.11.2022
- 85 Schreiber GB, Kimber MC. Source Plasma Donors: A Snapshot. 2017 Im Internet: https://www.pptaglobal.org/images/presentations/2017/Schreiber.AABBposterAbstract_Source_Plasma_Donors_A_Snapshot_2017_9.27.17.pdf; Stand: 04.11.2022
- 86 Rivera J, Lozano M. Plasmapheresis and Plasma Donation: Challenges in the Blood/Plasma Supply Chain. Plasmatology 2022; 16 26348535221107565 DOI: 10.1177/26348535221107565.