Sterile chromatography resin and use thereof in manufacturing processes

Patent metadata

Field	Value
Publication number	US-9630165-B2
Application number	US-201514629315-A
Country	US
Kind code	B2
Filing date	Feb 23, 2015
Priority date	Jan 17, 2014
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

Provided herein are methods of reducing bioburden of (e.g., sterilizing) a chromatography resin that include exposing a container including a composition including a chromatography resin and at least one antioxidant agent and/or chelator to a dose of gamma-irradiation sufficient to reduce the bioburden of the container and the chromatography resin, where the at least one antioxidant agent and/or chelator are present in an amount sufficient to ameliorate the loss of binding capacity of the chromatography resin after/upon exposure to the dose of gamma-irradiation. Also provided are reduced bioburden chromatography columns including the reduced bioburden chromatography resin, compositions including a chromatography resin and at least one chelator and/or antioxidant agent, methods of performing reduced bioburden column chromatography using one of these reduced bioburden chromatography columns, and integrated, closed, and continuous processes for reduced bioburden manufacturing of a purified recombinant protein.

First claim

What is claimed is:

1. A method of reducing bioburden of a chromatography resin comprising:
exposing a container comprising a composition comprising (i) a chromatography resin and (ii) a liquid comprising at least one chelator to a dose of gamma-irradiation sufficient to reduce the bioburden of the container and the chromatography resin, wherein the at least one chelator is present in an amount sufficient to ameliorate the loss of binding capacity of the chromatography resin after exposure to the dose of gamma-irradiation.

2. The method of claim 1 , wherein the container is a storage vessel.

3. The method of claim 1 , wherein the container is a chromatography column.

4. The method of claim 1 , wherein the container is a packed chromatography column.

5. The method of claim 1 , wherein the composition is a slurry of sedimented chromatography resin in the liquid.

6. The method of claim 5 , wherein the liquid is a buffered solution.

7. The method of claim 1 , wherein the at least one chelator is selected from the group consisting of: ethylenediaminetetraacetic acid (EDTA), 2,3-dimercapto-1-propanesulfonic acid sodium (DMPS), dimercaptosuccinic acid (DMSA), metallothionin, and desferroxamine.

8. The method of claim 1 , wherein the chromatography resin is selected from the group consisting of: an anion exchange chromatography resin, a cation exchange chromatography resin, an affinity chromatography resin, a hydrophobic interaction chromatography resin, and a size exclusion chromatography resin.

9. The method of claim 1 , wherein the dose is between about 15 kGy and about 45 kGy.

10. A method of reducing bioburden of a chromatography resin comprising:
exposing a container comprising a composition comprising a chromatography resin and at least one antioxidant agent to a dose of gamma-irradiation sufficient to reduce the bioburden of the container and the chromatography resin, wherein the at least one antioxidant agent is present in an amount sufficient to ameliorate the loss of binding capacity of the chromatography resin after exposure to the dose of gamma-irradiation.

11. The method of claim 10 , wherein the container is a storage vessel.

12. The method of claim 10 , wherein the container is a chromatography column.

13. The method of claim 10 , wherein the container is a packed chromatography column.

14. The method of claim 10 , wherein the composition further comprises at least one chelator.

15. The method of claim 10 , wherein the composition is a slurry of sedimented chromatography resin in a liquid comprising the at least one antioxidant agent.

16. The method of claim 10 , wherein the composition is a solid mixture.

17. The method of claim 10 , wherein the composition comprises at least one antioxidant agent selected from the group consisting of: reduced glutathione, reduced thioredoxin, reduced cysteine, a carotenoid, melatonin, lycopene, tocopherol, reduced ubiquinone, ascorbate, bilirubin, uric acid, lipoic acid, a flavonoid, a phenolpropanoid acid, lidocaine, naringenin, fullerene, glucose, histidine, methionine, mannitol, 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, and dimethylmethoxy chromanol.

18. The method of claim 15 , wherein the liquid is a buffered solution.

19. The method of claim 10 , wherein the chromatography resin is selected from the group consisting of: an anion exchange chromatography resin, a cation exchange chromatography resin, an affinity chromatography resin, a hydrophobic interaction chromatography resin, and a size exclusion chromatography resin.

20. The method of claim 10 , wherein the dose is between about 15 kGy and about 45 kGy.

21. A method of reducing bioburden of a chromatography resin comprising:
exposing a container comprising a composition comprising a chromatography resin and methionine and/or histidine to a dose of gamma-irradiation sufficient to reduce the bioburden of the container and the chromatography resin, wherein the methionine and/or histidine is present in an amount sufficient to ameliorate the loss of binding capacity of the chromatography resin after exposure to the dose of gamma-irradiation.

22. The method of claim 21 , wherein the composition comprises a chromatography resin and between 5 mM and about 150 mM methionine.

23. The method of claim 21 , wherein the composition comprises a chromatography resin and between about 5 mM and about 150 mM histidine.

24. The method of claim 21 , wherein the composition comprises a chromatography resin, between about 5 mM and about 150 mM methionine, and between about 5 mM and about 150 mM histidine.

25. The method of claim 21 , wherein the container is a storage vessel or a chromatography column.

26. The method of claim 21 , wherein the container is a packed chromatography column.

27. The method of claim 21 , wherein the composition is a solid mixture or a slurry of sedimented chromatography resin in a liquid comprising the methionine and/or histidine.

28. The method of claim 27 , wherein the liquid is a buffered solution.

29. The method of claim 21 , wherein the chromatography resin is selected from the group consisting of: an anion exchange chromatography resin, a cation exchange chromatography resin, an affinity chromatography resin, a hydrophobic interaction chromatography resin, and a size exclusion chromatography resin.

30. The method of claim 21 , wherein the dose is between about 15 kGy and about 45 kGy.

Assignees

• Genzyme Corp

Inventors

• Godawat Rahul
• Warikoo Veena
• Patil Rohan
• Konstantinov Konstantin
• Ryakala Venkat Kishore

Classifications

• B01D15/362

  Cation-exchange · CPC title

• B01J39/26

  Cation exchangers for chromatographic processes · CPC title

• B01J20/281

  Sorbents specially adapted for preparative, analytical or investigative chromatography · CPC title

• B01D15/1864 Primary

  using two or more columns · CPC title

• B01J20/265

  modified or post-treated polymers (polymer carriers or substrates subjected to further impregnating or coating B01J20/3208) · CPC title