Large Scale Production of Human Plasma Fractions

Abstract

Summary The modifications put on the alcohol fractionation procedure of Nitschmann., Kistler and Lergier [8] since 1954 are communicated. The yields and purities realised were calculated from the results of about 150 fractionation runs, 100 1 of plasma each. The actual method allows the isolation of 48% of the total plasmaproteins as albumin (98% pure in electrophoretic analysis), 9,8% as γ‐Globulin (practically 100% pure) and 3,4% as clottable fibrinogen. A scheme summarizes the details of the entire procedure. Résumé Les modifications apportées depuis 1954 à la méthode de fractionnement de Nitschmann, Kistler et Lergier [8] sont décrites. Le rendement et la pureté des differents fractions ont été calculées à partir des résultats de 150 fractionnements de 100 litres chacun. La méthode actuelle permet d'obtenir 48% des protéines plasmatiques totales sous forme d'albumine (degré de pureté électrophorétique de 98%), 9,8% sous forme de γ‐globuline (degré de pureté pratiquement de 100%) et 3,4% sous forme de fibrinogène coagulable. Un schéma détaillé risume l'ensemble du procédé de fractionnement. Zusammenfassung: Die seit 1954 vorgenommenen Veränderungen der Alkoholfraktionierungsmethode nach Nitschmann, Kistler und Lergier [8] werden dargelegt. Die mit der Methode praktisch erzielten Ausbeuten und Reinheiten wurden aus den Ergebnissen von and 150 100‐Liter‐Plasma‐Ansätzen ermittelt: Nnch dem heutigen Verfahren lassen sich etwa 48% der totalen Plasmaproteine als Albumin (ungefähr 98% elektrophoretisch rein), 9,80/, als γ‐Globulin (praktisch 100prozentig rein) und 3,4% als gerinnbares Fibrinogen gewinnen. Das ganze Fraktionierverfahren ist in Form eines detaillierten Schemas zusammenfassend dargestellt.

Development, Manufacturing and Characterization of a Highly Purified, Liquid Immunoglobulin G Preparation from Human Plasma

“…IVIG liquid SSI was produced from fraction II + III (precipitate B) obtained by the method of Kistler and Nitschmann [22]. Alternative starting materials, e.g.…”

“…The plasma was then processed by ethanol fractionation according to Kistler and Nitschmann [22]. Initially, fraction I + II + III was precipitated and used as starting material.…”

“…The first process for Ig isolation from human plasma was devised by Cohn et al [20]. This method used graduated ethanol fractionation, and was later modified by Oncley [21] and Kistler and Nitschmann [22]. The purity of the Ig preparations obtained by these methods was adequate for subcutaneous and intramuscular use but could give rise to side effects due to impurities and aggregated or denatured antibody molecules, especially if given intravenously [23,24,25,26,27,28].…”

Optimization Considerations for the Purification of α1‐Antitrypsin Using Silica‐Based Ion‐Exchange Adsorbents in Packed and Expanded Beds

“…The cryoprecipitate is recovered to produce the anti-hemophilia factor, Factor VIII, and the cryosupernatant is then used to produce (12) various therapeutic coagulation factors (Factor IX, Factor VII, antithrombin III, etc.). Typically, the cryosupernatant is subjected to an ethanol fractionation procedure, resulting in the formation of the Cohn Fraction IV-I, or to a modified procedure (13), leading to the formation of the so-called Fraction A+1. This Fraction A+1 is equivalent to the Cohn Fraction I+II+III, and is enriched in immunoglobulins (IgG)s, haptoglobulin, antithrombin III, ceruloplasmin, and albumin, among other therapeutically valuable proteins.…”

Latex Particle Agglutination in the Immunochemical System Human Serum Albumin–Anti‐Human Serum Albumin Rabbit Serum

“…Crude human serum albumin was prepared from the pooled human plasma by the method described by Kistler and Nitschmann [13]. The crystalline sample was obtained by fractional salting out with ammonium sulfate [14] in four steps.…”