Methods for making stable protein compositions

A method for preparing a purified protein, the method comprises:

• (a) subjecting a sample comprising a protein of interest to a purification process to obtain a preparation comprising the protein of interest,
• (b) conducting a final ultrafiltration and diafiltration operation consisting of (i) adjusting the pH of the preparation produced by step (a) to a target pH using a pH adjusting agent prior to performing the ultrafiltration and diafiltration step, wherein the target pH is from pH 4.0 to pH 7.0, and (ii) performing the final ultrafiltration and diafiltration step in a medium that comprises a buffer, wherein the pH adjusting agent is (A) an acid selected from the group consisting of acetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzene sulfonic acid, benzoic acid, boric acid, camphorsulfonic acid, caprylic acid, formic acid, glutamic acid, hydrochloride acid, hydrobromic acid, hydroxy acids, hyaluronic acid, methanesulfonic acid, nitric acid, propionic acid, sulfuric acid, sulfonic acid, transexamic acid, and tartaric acid;
• (B) a base selected from the group consisting of ammonia solution, ammonium carbonate, diethanolamine, calcium hydroxide, ethanolamine, lysine, meglumine, poly-lysine, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide, and triethanolamine;
• or (C) a buffer selected from the group consisting of acetate buffer, aspartate buffer, ascorbate buffer, borate buffer, benzoate buffer, carbonate buffer, citrate buffer, glycine buffer, HEPES buffer, MOPS buffer, MES buffer, N-(2-acetamido)iminodiacetic acid (ADA) buffer, histidine buffer, lactate buffer, phosphate buffer, succinate buffer, Tris buffer, Bis-tris buffer, and tartrate buffer;
• and
• (c) recovering a composition comprising the protein from the final ultrafiltration and diafiltration operation, wherein the target pH is within 0.2 pH units of the pH of the composition comprising the protein recovered from the final ultrafiltration and diafiltration operation.