Manufacture of Degarelix

A method of preparing a lyophilized degarelix drug substance, comprising:

• a. purifying degarelix as obtained by liquid or solid phase peptide synthesis to obtain a degarelix solution with a purity of at least 95%, as determined by high-performance liquid chromatography (HPLC);
• b. isolating the degarelix solution via lyophilization to obtain isolated degarelix;
• c. dissolving the isolated degarelix to obtain a reconstituted degarelix solution, wherein the reconstituted degarelix solution of step (c) has a degarelix concentration ranging from 10 to 20 g degarelix/L of aqueous 2% acetic acid;
• and
• d. lyophilizing the reconstituted degarelix solution to provide the lyophilized degarelix drug substance,
• wherein the lyophilized degarelix drug substance has a viscosity of less than 3.2 mPas, as determined upon dissolution in 1 mL of aqueous 2.5% (w/V) mannitol solution of an amount of the lyophilized degarelix drug substance necessary to achieve a degarelix concentration of 20 mg/mL;
• and wherein the lyophilized degarelix drug substance has an acetic acid concentration ranging from 4.5% to 10.00% (w/w) and a water content of 10% (w/w) or less.

A method of preparing a degarelix drug substance, comprising the following steps a, b, and d;

• or a, c, and d:
• a. purifying degarelix as obtained by liquid or solid phase peptide synthesis to obtain a degarelix solution with a purity of at least 95%, as determined by high-performance liquid chromatography (HPLC);
• and
• b. evaporating a solvent to concentrate the degarelix solution to obtain aggregated degarelix and deaggregating the aggregated degarelix with acetic acid;
• c. loading the degarelix solution onto a chromatographic column and eluting degarelix from the column with acetic acid;
• d. isolating the degarelix via spray drying to provide the degarelix drug substance, and
• wherein the degarelix drug substance has a viscosity of less than 3.2 mPas, as determined upon dissolution in 1 mL of aqueous 2.5% (w/V) mannitol solution of an amount of the degarelix drug substance necessary to achieve a degarelix concentration of 20 mg/mL;
• and wherein the degarelix drug substance has an acetic acid concentration ranging from 4.5% to 10.00% (w/w) and a water content of 10% (w/w) or less.

A method of preparing a degarelix drug substance, comprising:

• a. purifying degarelix as obtained by liquid or solid phase peptide synthesis to obtain a degarelix solution with a purity of at least 95%, as determined by high-performance liquid chromatography (HPLC);
• and
• b. isolating the degarelix via spray drying to provide the degarelix drug substance, wherein the degarelix drug substance provided has a viscosity of less than 3.2 mPas, as determined upon dissolution in 1 mL of aqueous 2.5% (w/V) mannitol solution of an amount of the degarelix drug substance necessary to achieve a degarelix concentration of 20 mg/mL;
• and wherein said degarelix drug substance has an acetic acid concentration ranging from 4.5% to 10.00% (w/w) and a water content of 10% (w/w) or less.