Stable lyophilized pharmaceutical preparations of monoclonal or polyclonal antibodies

Abstract

The invention concerns lyophilized pharmaceutical preparations of monoclonal or polyclonal antibodies which contain a sugar or an amino sugar, an amino acid and a surfactant as stabilizers. In addition the invention concerns a process for the production of this stable lyophilisate as well as the use of a sugar or amino sugar, an amino acid and a surfactant as stabilizers for therapeutic or diagnostic agents containing antibodies.

1 . A stable lyophilized pharmaceutical preparation of monoclonal or polyclonal antibodies, comprising
 a) sucrose in a concentration of 35 mg/ml to 75 mg/ml,   b) arginine or ornithine in a concentration of 10 mg/ml to 25 mg/ml,   c) Tween 20 (Polyethylene glycol sorbitan monolaurate) or Pluronic F68 (polyoxyethylene-polyoxypropylene polymer) in a concentration of 0.1 mg/ml, and   d) monoclonal or polyclonal antibodies at a concentration up to 20 mg/ml.   
     
     
         2 . The preparation according to  claim 1 , wherein the preparation is essentially free of polyethylene glycols and/or free of protein-like standard pharmaceutical auxiliary substances. 
     
     
         3 . The preparation according to  claim 1 , wherein it comprises physiologically tolerated auxiliary substances selected from the group consisting of acids, bases, buffers and isotonizing agents. 
     
     
         4 . An aqueous pharmaceutical preparation of monoclonal or polyclonal antibodies obtainable by redissolving the lyophilisate according to  claim 1 . 
     
     
         5 . An aqueous pharmaceutical preparation according to  claim 4 , wherein the solution has a pH value of 5-8. 
     
     
         6 . The preparation according to  claim 4 , wherein the solution has a pH value of 6-7.4. 
     
     
         7 . A stable lyophilized pharmaceutical preparation of monoclonal or polyclonal antibodies, comprising
 a) sucrose in a concentration of 35 mg/ml to 75 mg/ml,   b) arginine or ornithine in a concentration of 10 to 25 mg/ml,   c) a surfactant in a concentration of 0.05 to 5 mg/ml, and   d) monoclonal or polyclonal antibodies at a concentration up to 20 mg/ml,   
       wherein said stable lyophilized pharmaceutical preparation does not exhibit any detectable degradation products or protein aggregates when stored at a temperature of 18-23° C. for a time period of at least 1 to 2 years. 
     
     
         8 . The stable lyophilized pharmaceutical preparation according to  claim 7 , wherein said preparation does not exhibit any detectable degradation products or protein aggregates when subjected to multiple freezing and thawing processes. 
     
     
         9 . The stable lyophilized pharmaceutical preparation according to  claim 1 , wherein the concentration of the antibodies is up to 8 mg/ml. 
     
     
         10 . The stable lyophilized pharmaceutical preparation according to  claim 9 , wherein the concentration of the antibodies is between 0.25 mg/ml to 8 mg/ml. 
     
     
         11 . A stable lyophilized pharmaceutical preparation of monoclonal or polyclonal antibodies, comprising
 a) sucrose in a concentration of from 35 mg/ml to 75 mg/ml,   b) arginine or ornithine in a concentration of 10 to 25 mg/ml,   c) polyoxyethylene-polyoxypropylene polymer in a concentration of 0.05 to 5 mg/ml, and   d) monoclonal or polyclonal antibodies,   
       wherein the concentration of the antibodies is up to 8 mg/ml, and wherein said stable lyophilized pharmaceutical preparation does not exhibit any detectable degradation products or protein aggregates when stored at a temperature of 20° C. for a time period of two years.