Method to produce a highly concentrated immunoglobulin preparation for subcutaneous use

A method for preparing a composition of concentrated IgG from plasma, comprising:

• a) precipitating a cryo-poor plasma fraction, in a first precipitation step, with about 8% alcohol (v/v) at a pH of from 7.0 to 7.5 to obtain a first precipitate and a first supernatant;
• b) precipitating IgG from the first supernatant, in a second precipitation step, with from 20% to 25% alcohol (v/v) at a pH of from 6.8 to 7.2 to form a second precipitate and a second supernatant;
• c) suspending the second precipitate to form a suspension;
• d) adding fumed silica to the suspension and mixing the fumed silica with the suspension;
• e) filtering the suspension after the mixing in step d) to form a third supernatant containing IgG;
• f) further purifying IgG from the third supernatant to form an enriched IgG composition, wherein the further purifying comprises ion exchange chromatography;
• g) concentrating the enriched IgG composition to a protein concentration of from 2% to 10% (w/v) to form a first ultrafiltrate;
• h) diafiltering the first ultrafiltrate against a formulation buffer to form a diafiltrate;
• and
• i) concentrating the diafiltrate to a protein concentration of at least 20%, thereby preparing a composition of concentrated IgG from plasma.