Manufacture of degarelix
The present invention provides methods for producing a lyophilized degarelix product which, upon reconstitution with water for injection in an amount of 20 mg/ml, shows a viscosity of up to 15 mPas. The present invention also provides a lyophilized degarelix drug substance which shows, upon dissolution in water in an amount of 20 mg/ml, a viscosity of up to 3.2 mPas, a and processes for providing this lyophilized degarelix drug substance.
1. A lyophilized degarelix drug substance consisting of degarelix, 4.5% to 10.00% (w/w) acetic acid, up to 10% (w/w) water, and, optionally, impurities due to its production process, wherein the lyophilized degarelix drug substance has a viscosity of up to 3.2 mPas, as determined upon dissolution in an amount of 20 mg degarelix free base in 1 ml of water containing 2.5% (w/V) mannitol.
2. The lyophilized degarelix drug substance of claim 1 , wherein the lyophilized degarelix drug substance has a viscosity ranging from 1.15 to 2.0 mPas, as determined upon dissolution in an amount of 20 mg degarelix free base in 1 ml of water containing 2.5% (w/V) mannitol.
3. The lyophilized degarelix drug substance of claim 2 , wherein the viscosity is determined 240 minutes after production of the lyophilized degarelix drug substance.
4. The lyophilized degarelix drug substance of claim 1 , wherein the lyophilized degarelix drug substance shows an optical density of 0 . 10 AU or less at a concentration of 20 mg degarelix free base/ml in 2.5% (w/V) aqueous mannitol.
5. The lyophilized degarelix drug substance of claim 4 , wherein the optical density is determined 240 minutes after production of the lyophilized degarelix drug substance.
6. A solution of degarelix, prepared by a reconstitution process consisting of reconstituting a lyophilized degarelix drug substance with a solvent consisting of water for injection consisting of water and, optionally, mannitol, to a degarelix concentration selected from 5 mg/ml, 15 mg/ml, 25 mg/ml, and 35 mg/ml of degarelix,
wherein the lyophilized degarelix drug substance consists of degarelix, 4.5% to 10.00% (w/w) acetic acid, up to 10% (w/w) water, and, optionally, impurities due to its production process, wherein the lyophilized degarelix drug substance has a viscosity of up to 3.2 mPas, as determined upon dissolution in an amount of 20 mg degarelix free base in 1 ml of water containing 2.5% (w/V) mannitol.
7. The lyophilized degarelix drug substance of claim 1 , containing impurities due to its production process.
8. The lyophilized degarelix drug substance of claim 1 , consisting of degarelix, 4.5% to 10.00% (w/w) acetic acid, and up to 10% (w/w) water.
9. The solution of claim 6 , wherein the lyophilized degarelix drug substance consists of degarelix, 4.5% to 10.00% (w/w) acetic acid, and up to 10% (w/w) water.
10. The solution of claim 6 , wherein the lyophilized degarelix drug substance contains impurities due to its production process.
11. The solution of claim 6 , wherein the reconstituting solvent consists of water for injection.