Method to produce a highly concentrated immunoglobulin preparation for subcutaneous use

摘要

The present invention relates to a new and improved method for preparing a highly concentrated immunoglobulin composition from pooled plasma for subcutaneous injection. A composition comprising 20% or more immunoglobulin suitable for subcutaneous use is also described.

主权项

1. A method for preparing a concentrated immunoglobulin G (IgG) composition, comprising the steps:
(A) concentrating a first solution comprising IgG to a protein concentration of from 2% to 10% (w/v) by ultrafiltration using a first ultra-/diafiltration system comprising a first ultrafiltration membrane having a nominal molecular weight cut off (NMWCO) of 100 kDa or less, thereby forming a first IgG concentrate, wherein at least 95% of protein in the first solution is IgG; (B) diafiltering the first IgG concentrate against a diafiltration buffer using the first ultra-/diafiltration system comprising the first ultrafiltration membrane, thereby forming a first IgG diafiltrate; (C) concentrating the first IgG diafiltrate to a protein concentration of greater than 20% (w/v) by ultrafiltration using the first ultra-/diafiltration system comprising the first ultrafiltration membrane, thereby forming a second IgG concentrate; (D) collecting the second IgG concentrate from the first ultra-/diafiltration system; (E) washing the first ultrafiltration membrane by re-circulating a post-wash buffer through the first ultra-/diafiltration system wherein the first ultra-/diafiltration system is washed with a volume of post-wash buffer equal to at least two times the dead volume of the first ultra-/diafiltration system, thereby forming a first IgG post-wash solution; (F) transferring the first IgG post-wash solution from the first ultra-/diafiltration system into a second ultra-/diafiltration system comprising a second ultrafiltration membrane having a nominal molecular weight cut off (NMWCO) of 100 kDa or less, wherein the surface area of the second ultrafiltration membrane is lower than the surface area of the first ultrafiltration membrane; (G) concentrating the first IgG post-wash solution to a protein concentration of greater than 20% (w/v) by ultrafiltration using the second ultra-/diafiltration system comprising a second ultra-/diafiltration membrane, thereby forming a third IgG concentrate; and (H) combining the third IgG concentrate from the second ultra-/diafiltration system with the second IgG concentrate, thereby forming a concentrated IgG composition.