Methods for sterilizing preparations of monoclonal immunoglobulins

Abstract

Methods are disclosed for sterilizing preparation of monoclonal immunoglobulins to reduce the level of active biological contaminants such as viruses, bacteria, yeasts, molds, mycoplasmas, prions and parasites.

1 - 66 . (canceled)  
     
     
         66 . A method for sterilizing a preparation of monoclonal immunoglobulins that is sensitive to radiation and that has a residual solvent content, comprising: 
 (i) reducing said residual solvent content of said preparation to a level effective to protect said preparation from said radiation; and    (ii) irradiating said preparation with gamma radiation at an effective rate for a period of time effective to sterilize said preparation.    
     
     
         67 . A method for sterilizing a preparation of monoclonal immunoglobins that is sensitive to radiation, comprising: 
 (i) adding to said preparation at least one stabilizer in an amount effective to protect said preparation from said radiation; and    (ii) irradiating said preparation with gamma radiation at an effective rate for a period of time effective to sterilize said preparation.    
     
     
         68 . A method for sterilizing a preparation of monoclonal immunoglobulins that is sensitive to radiation and that has a residual solvent content, comprising: 
 (i) reducing said residual solvent of said preparation to a level effective to protect said preparation from said preparation from said radiation;    (ii) adding to said preparation at least one stabilizer in an amount effective to protect said preparation from said radiation; and    (iii) irradiating said preparation with gamma radiation at an effective rate for a period of time effective to sterilize said preparation, wherein steps (i) and (ii) may be performed in inverse order.    
     
     
         69 . The method according to any one of claims  66 ,  67  and  68 , wherein said monoclonal immunoglobulins are selected from the group consisting of IgG, IgM, IgA, IgD, IgE and fragments, derivatives, metabolites and mixtures IgG, IgM, IgA, IgD and IgE.  
     
     
         70 . The method according to any one of claims  66 ,  67  and  68 , wherein said monoclonal immunoglobulins comprise immunoglobulin fragments selected from the group consisting of F(ab′)2, Fab′, Fab, Fc, Facb, pFc′, Fd and metabolites and derivatives of F(ab′)2, Fab′, Fab, Fc, Facb, pFc′ and Fd.  
     
     
         71 . The method according to any one of claims  66 ,  67  and  68 , wherein said residual solvent content is reduced by at least one method selected from the group consisting of lyophilization, drying, concentration, addition of solute, evaporation, chemical extraction, spray-drying and vitrification.  
     
     
         72 . The method according to  claim 67  or  claim 68 , wherein said at least one stabilizer is selected from the group consisting of ascorbic acid or a salt or ester thereof; glutathione; 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; uric acid or a salt or ester thereof; methionine; histidine; N-acetyl cysteine; lipoic acid; sodium formaldehyde sulfoxylate; gallic acid or a derivative thereof; propyl gallate; and combinations thereof.  
     
     
         73 . The method according to any one of claims  66 ,  67  and  68 , wherein said irradiating is conducted at a temperature below ambient temperature.