title: Minipool caprylic acid fractionation of plasma using disposable equipment: a practical method to enhance immunoglobulin supply in developing countries.
abstract: BACKGROUND
  Immunoglobulin G (IgG) is an essential plasma-derived medicine that is lacking in developing countries. IgG shortages leave immunodeficient patients without treatment, exposing them to devastating recurrent infections from local pathogens. A simple and practical method for producing IgG from normal or convalescent plasma collected in developing countries is needed to provide better, faster access to IgG for patients in need.
  
  
  RESULTS
  IgG was purified from 10 consecutive minipools of 20 plasma donations collected in Egypt using single-use equipment. Plasma donations in their collection bags were subjected to 5%-pH5.5 caprylic acid treatment for 90 min at 31°C, and centrifuged to remove the precipitate. Supernatants were pooled, then dialyzed and concentrated using a commercial disposable hemodialyzer. The final preparation was filtered online by gravity, aseptically dispensed into storage transfusion bags, and frozen at <-20°C. The resulting preparation had a mean protein content of 60.5 g/L, 90.2% immunoglobulins, including 83.2% IgG, 12.4% IgA, and 4.4% IgM, and residual albumin. There was fourfold to sixfold enrichment of anti-hepatitis B and anti-rubella antibodies. Analyses of aggregates (<3%), prekallicrein (5-7 IU/mL), plasmin (26.3 mU/mL), thrombin (2.5 mU/mL), thrombin-like activity (0.011 U/g), thrombin generation capacity (< 223 nM), and Factor XI (<0.01 U/mL) activity, Factor XI/XIa antigen (2.4 ng/g) endotoxin (<0.5 EU/mL), and general safety test in rats showed the in vitro safety profile. Viral validation revealed >5 logs reduction of HIV, BVDV, and PRV infectivity in less than 15 min of caprylic acid treatment.
  
  
  CONCLUSIONS
  90% pure, virally-inactivated immunoglobulins can be prepared from plasma minipools using simple disposable equipment and bag systems. This easy-to-implement process could be used to produce immunoglobulins from local plasma in developing countries to treat immunodeficient patients. It is also relevant for preparing hyperimmune IgG from convalescent plasma during infectious outbreaks such as the current Ebola virus episode.
authors.affiliation: Shabrawishi Blood Bank, Shabrawishi Hospital, Cairo, Egypt.
authors.forename: Magdy
authors.initials: M
authors.lastname: El-Ekiaby
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Mariángela
authors.initials: M
authors.lastname: Vargas
authors.affiliation: Environmental and Food Pollutant Laboratory, Fayoum University, Fayoum, Egypt.
authors.forename: Makram
authors.initials: M
authors.lastname: Sayed
authors.affiliation: Shabrawishi Blood Bank, Shabrawishi Hospital, Cairo, Egypt.
authors.forename: George
authors.initials: G
authors.lastname: Gorgy
authors.affiliation: Saskatoon Cancer Center, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: Hadi
authors.initials: H
authors.lastname: Goubran
authors.affiliation: Human Protein Process Sciences, Lille, France.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Radosevic
authors.affiliation: Graduate Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Thierry
authors.initials: T
authors.lastname: Burnouf
mesh_terms: D000818:Animals; D001771:Blood Banks; D001782:Blood Donors; D002210:Caprylates / Q000737:chemistry*; D005591:Chemical Fractionation / Q000295:instrumentation*; D003906:Developing Countries; D004209:Disposable Equipment; D004534:Egypt; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000302:isolation & purification*; D010949:Plasma; D051381:Rats
chemical_list: D002210:Caprylates; D007074:Immunoglobulin G; C031492:octanoic acid