Immunoglobulin preparation and storage system for an immunoglobulin preparation
The present invention relates to an immunoglobulin preparation comprising immunoglobulin in a mass-volume percentage of at least 4%, wherein the concentration of oxygen dissolved in the preparation at room temperature is less than 40 μmol/l.
1. A ready-to-use liquid immunoglobulin preparation for intravenous or subcutaneous administration comprising immunoglobulin in a mass-volume percentage of at least 4%, wherein the concentration of oxygen dissolved in the preparation at room temperature is less than 200 μmol/l, wherein the absorbance at 350 nm minus the absorbance at 500 nm (absorbance A 350-500 nm ) of the immunoglobulin preparation remains below 0.28 upon storage for 24 months at 25° C. in the dark, and wherein the preparation is comprised within a container with a headspace occupied by a gas other than air, wherein the content of oxygen in the gas of the headspace remains less than 20 vol-% during said storage.
2. The immunoglobulin preparation according to claim 1 , wherein the concentration of oxygen dissolved in the preparation at room temperature is less than 175 μmol/l.
3. The immunoglobulin preparation according to claim 1 , wherein the immunoglobulin preparation comprises immunoglobulin in a mass-volume percentage of at least 5%.
4. The immunoglobulin preparation according to claim 1 , wherein the immunoglobulin comprised in the immunoglobulin preparation consists essentially of IgG.
5. The immunoglobulin preparation according to claim 1 , wherein the preparation has a mean increase in absorbance A 350-500 nm of less than 0.2 upon storage of 6 months at 37° C. in the dark.
6. Storage system for a ready-to-use liquid immunoglobulin preparation for intravenous or subcutaneous administration comprising a container having an interior, a first portion of said interior being occupied by the ready-to-use liquid immunoglobulin preparation comprising immunoglobulin in a mass-volume percentage of at least 4%, and the remaining portion of said interior forming a headspace and being occupied by a gas other than air, wherein the content of oxygen in the gas of the headspace is less than 20 vol-%, and wherein the absorbance A 350-500 nm of the immunoglobulin preparation in the container remains below 0.28 upon storage for 24 months at 25° C. in the dark.
7. The storage system according to claim 6 , wherein the content of oxygen in the gas of the headspace is less than 16 vol-%.
8. The storage system according to claim 6 , wherein the gas of the headspace is at approximately atmospheric or higher than atmospheric pressure.
9. The storage system according to claim 6 , wherein the content of inert gas in the gas of the headspace is more than 80 vol-%.
10. The storage system according to claim 6 , wherein the container is a vial.
11. The storage system according to claim 6 , wherein the headspace and the immunoglobulin preparation are in a volume ratio that ranges from 0.1:1 to 0.9:1.
12. The storage system according to claim 6 , wherein the storage system has a mean monthly increase of absorbance A 350-500 nm that is at least 10% lower than the mean monthly increase of absorbance A 350-500 nm observed when air is used as the gas in the headspace.
13. Process for preparing a storage system for an immunoglobulin preparation, comprising filing a container with the immunoglobulin preparation according to claim 1 , filling the container with a gas other than air, and sealing the container, wherein the gas forms a headspace above the preparation, and wherein the gas of the headspace has an oxygen content of less than 20 vol-%.
14. The process according to claim 13 , wherein the gas filled into the container is at atmospheric pressure.
15. The process according to claim 13 , wherein the immunoglobulin preparation comprises immunoglobulin in a solvent, and wherein the process comprises subjecting the immunoglobulin and/or its solvent to a degassing step and/or a gassing step using an inert gas.
16. The process according to claim 15 , wherein the solvent is subjected to the degassing and/or gassing step using an inert gas prior to formulation of the preparation.
17. The immunoglobulin preparation according to claim 1 , wherein the immunoglobulin preparation comprises immunoglobulin in a mass-volume percentage of 14-20%.
18. The immunoglobulin preparation according to claim 1 , wherein the immunoglobulin preparation comprises immunoglobulin in a mass-volume percentage of at least 18%.
19. The immunoglobulin preparation according to claim 1 , wherein the immunoglobulin preparation comprises immunoglobulin in a mass-volume percentage of at least 20%.