Process for Producing a Plasma Protein-Containing Medicament

Abstract

There is disclosed a method of preparing a plasma protein-containing medicament from citrated plasma or from a citrate-containing plasma fraction, the medicament being substantially free from undesired metals, which method comprises the following steps exchanging the citrate and optionally citrate-bound metals in a plasma-protein-containing solution for a water-soluble mono- or dicarboxylate or for an organic mono- or dicarboxylic acid under non-precipitating conditions, recovering the plasma protein or the plasma proteins, and finishing the medicament.

1 - 13 . (canceled) 
     
     
         14 . A plasma-protein-containing medicament obtained from citrated plasma or from a citrate-containing plasma fraction, wherein the medicament has a reduced concentration of undesired metals selected from the group consisting of aluminum, cadmium, zinc, lead and iron, wherein the medicament is obtained by a method comprising the steps of:
 (a) obtaining citrated plasma or citrate-containing plasma fraction by Cohn fractionation;   (b) adding to the citrated plasma or citrate-containing plasma fraction a compound to achieve a solution having a compound concentration of between 0.001 and 1.00 mol/liter, wherein the compound is selected from the group consisting of a monocarboxylate, a dicarboxylate, a monocarboxylic acid and a dicarboxylic acid;   (c) exchanging citrate and citrate-bound metals that may be present in the plasma or plasma fraction with the compound by diafiltration, ultrafiltration or chromatography at a temperature above 0° C. to 50° C. and at a pH of 6 to 8, under non-precipitating conditions, thereby reducing the concentration of citrate and the undesired metals that may have been present;   (d) recovering one or more plasma proteins; and   (e) finishing the medicament.   
     
     
         15 . The plasma-protein-containing medicament as set forth in  claim 14 , wherein the compound has 2 to 20 carbon atoms. 
     
     
         16 . The plasma-protein-containing medicament as set forth in  claim 14 , wherein the compound is selected from the group consisting of caprylate, tartrate, hexanoic acid and acetate. 
     
     
         17 . The plasma-protein-containing medicament as set forth in  claim 14 , wherein the plasma proteins for the medicament are selected from the group consisting of albumin, coagulation factors, fibrinolysis factors, immunoglobulins and glycoproteins. 
     
     
         18 . The plasma-protein-containing medicament as set forth in  claim 14 , wherein the medicament has a content of undesired metals of less than 100 μg/l. 
     
     
         19 . The plasma-protein-containing medicament as set forth in  claim 14 , wherein the medicament has a content of undesired metals of less than 10 μg/l. 
     
     
         20 . The plasma-protein-containing medicament as set forth in  claim 14 , wherein the content of undesired metals is less than 200 ng/l. 
     
     
         21 . A plasma-protein-containing medicament obtained from a Cohn fraction comprising plasma proteins and citrate, wherein the medicament has a reduced concentration of undesired metals selected from the group consisting of aluminum, cadmium, zinc, lead and iron, wherein the medicament is obtained by a method comprising the steps of:
 (a) adding to the Cohn fraction, a compound to achieve a solution having the compound concentration of between 0.001 and 1.00 mol/liter, wherein the compound is selected from the group consisting of a monocarboxylate, a dicarboxylate, a monocarboxylic acid and a dicarboxylic acid;   (b) exchanging the citrate and citrate-bound metals that may be present in the Cohn fraction with the compound by diafiltration, ultrafiltration or chromatography at a temperature above 0° C. to 50° C. and at a pH of 6 to 8, under non-precipitating conditions, thereby reducing the concentration of citrate and undesired metals that may have been present;   (c) recovering one or more plasma proteins; and   (d) finishing the medicament.   
     
     
         22 . The plasma-protein-containing medicament as set forth in  claim 21 , wherein the compound has 2 to 20 carbon atoms. 
     
     
         23 . The plasma-protein-containing medicament as set forth in  claim 21 , wherein the compound is selected from the group consisting of caprylate, tartrate, hexanoic acid and acetate. 
     
     
         24 . The plasma-protein-containing medicament as set forth in  claim 21 , wherein the plasma proteins for the medicament are selected from the group consisting of albumin, coagulation factors, fibrinolysis factors, immunoglobulins and glycoproteins. 
     
     
         25 . The plasma-protein-containing medicament as set forth in  claim 21 , wherein the medicament has a content of undesired metals of less than 100 μg/l. 
     
     
         26 . The plasma-protein-containing medicament as set forth in  claim 21 , wherein the medicament has a content of undesired metals of less than 10 μg/l. 
     
     
         27 . The plasma-protein-containing medicament as set forth in claim wherein the medicament has a content of undesired metals of less than 200 ng/l.