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 . A method of preparing a plasma-protein-containing medicament from citrated plasma or from a citrate-containing plasma fraction, which medicament is substantially free from undesired metals and also does not take up any metals when stored in metal-containing containers, 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.    
     
     
         2 . A method according to  claim 1 , characterized in that as the plasma-protein-containing medicament, a medicament comprising one or several plasma proteins selected from the group consisting of the factors of coagulation and fibrinolysis, immunoglobulins, glycoproteins and albumin is prepared.  
     
     
         3 . A method according to  claim 1  or  2 , characterized in that a salt of an organic carboxylic acid having 2 to 20 carbon atoms is used for exchanging the citrate.  
     
     
         4 . A method according to any one of  claims 1  to  3 , characterized in that a caprylate and/or a tartrate is used for exchanging the citrate.  
     
     
         5 . A method according to any one of  claims 1  to  3 , characterized in that an organic mono- or dicarboxylic acid having 2 to 4 carbon atoms is used for exchanging the citrate.  
     
     
         6 . A method according to any one of  claims 1  to  5 , characterized in that a plasma-protein-containing medicament which is substantially free from aluminum is prepared.  
     
     
         7 . A method according to any one of  claims 1  to  6 , characterized in that exchanging of the citrate is effected during a diafiltration, ultrafiltration, a gel permeation chromatography or a chromatographic separation method, respectively, which enable the separation of the protein from salts.  
     
     
         8 . A method according to any one of  claims 1  to  7 , characterized in that before the exchange, the plasma-protein-containing solution is purified and/or concentrated.  
     
     
         9 . A method according to any one of  claims 1  to  8 , characterized in that the plasma-protein-containing solution is treated, preferably heat-treated, before and/or after the exchange, so as to inactivate possibly present viruses.  
     
     
         10 . A method according to any one of  claims 1  to  9 , characterized in that the virus inactivation treatment is effected immediately after the recovery of the plasma protein in the presence of the mono- or dicarboxylate.  
     
     
         11 . A method according to any one of  claims 1  to  10 , characterized in that finishing of the medicament is effected exclusively with citrate-free components.  
     
     
         12 . A method according to any one of  claims 1  to  11 , characterized in that the exchange of the citrate is effected in the presence of sodium chloride, preferably with an at least 4% by weight sodium chloride solution.  
     
     
         13 . A plasma-protein-containing medicament obtainable according to a method according to any one of  claims 1  to  12 , having a content of undesired metals, in particular aluminum, of less than 100 μg/l, preferably less than 10 μg/l, in particular less than 200 ng/l.