Methods for sterilizing biological materials

• US 6,946,098 B2
• Filed: 08/10/2001
• Issued: 09/20/2005
• Est. Priority Date: 08/10/2001
• Status: Expired due to Fees

• Current Assignee: Clearant, Inc.
• Original Assignee: Clearant, Inc.
• Inventors: Burgess, Wilson, Mann, David M., Drohan, William N., MacPhee, Martin J., Griko, Yuri, Miekka, Shirley I.
• Primary Examiner(s): MCKANE, ELIZABETH L
• Application Number:
  US09/925,620
• Publication Number:
  US 20030031581A1
• Time in Patent Office: 1,502 Days
• Field of Search: 422/22, 422/28, 435/2
• US Class Current: 422/22
• CPC Class Codes: A23L 3/263 with corpuscular or ionising radiation, i.e. X, alpha, beta or omega radiation laser plasma radiation A23L3/26
• CPC Class Codes: A61L 2/0011 using physical methods
• CPC Class Codes: A61L 2/0029 Radiation
• CPC Class Codes: A61M 1/3681 by irradiation
• CPC Class Codes: A61M 1/3683 using photoactive agents
• CPC Class Codes: A61M 1/3686 by removing photoactive agents after irradiation

Abstract

Methods are disclosed for sterilizing biological materials to reduce the level therein of one or more biological contaminants or pathogens, such as prions, responsible for the disease states known as transmissible spongiform encephalopathies (TSEs) in mammals. These methods involve sterilizing biological materials with irradiation.

Claims

1. A composition comprising at least one biological material and at least one stabilizer in an amount effective to preserve said biological material for sterilization with radiation, wherein said biological material is glassy or vitrified.

2. The composition according to claim 1, wherein said at least one stabilizer is selected from the group consisting of polyhydric alcohols, DMSO and mixtures thereof.

3. The composition according to claim 2, wherein said polyhydric alcohols are selected from the group consisting of trehalose, mannitol, glycerol and combinations thereof.

4. The composition according to claim 1, wherein said at least one stabilizer comprises trehalose.

5. The composition according to claim 1, wherein said at least one stabilizer comprises a polyhydric alcohol.

6. The composition according to claim 1, wherein said at least one stabilizer comprises glycerol.

7. The composition according to claim 1, wherein said at least one stabilizer comprises mannitol.

8. The composition according to claim 1, wherein said at least one stabilizer comprises DMSO.

17. The composition of claim 1 or 9, wherein said biological material is selected from the group consisting of monoclonal immunoglobulins, polyclonal immunoglobulins, glycosidases, sulfatases, urokinase and Factor VIII.

18. The composition according to claim 1 or 9, wherein said biological material is selected from the group consisting of cells, tissues, blood, blood components, proteins, enzymes, immunoglobulins, botanicals, food, ligaments, tendons, nerves, bone, demineralized bone matrix, grafts, joints, femurs, femoral heads, teeth, skin grafts, bone marrow, heart valves, cartilage, corneas, arteries, veins, meat, organs, limbs, digits, lipids, carbohydrates, collagen, chitin, stem cells, islet of Langerhans cells, genetically altered cells, red blood cells, white blood cells, proteinaceous material and combinations thereof.

19. The composition according to claim 18, wherein said blood components are selected from the group consisting of cellular blood components, blood proteins, liquid blood components and combinations thereof.

20. The composition according to claim 18, wherein said collagen is selected from the group consisting of native collagen, afibrillar collagen, atelomeric collagen, soluble collagen and insoluble collagen.

21. The composition according to claim 18, wherein said biological material comprises a protein or peptide produced from cell culture.

22. The composition according to claim 1 or 9, wherein said biological material is whole or processed.

23. The composition according to claim 1 or 9, wherein said biological material is selected from the group consisting of hearts, livers, lungs, kidneys, intestines and pancreas.

24. The composition according to claim 1 or 9, wherein said biological material is human.

25. The composition according to claim 1 or 9, wherein said biological material is mammalian.

26. The composition according to claim 1 or 9, wherein said biological material is bovine.

27. The composition according to claim 1 or 9, wherein said biological material is equine.

28. The composition according to claim 1 or 9, wherein said biological material is porcine.

29. The composition according to claim 1 or 9, wherein said biological material is transgenic or recombinant.

30. The composition according to claim 29, wherein said biological material is milk.

31. The composition according to claim 1 or 9, wherein said biological material is milk, collagen, plasma or serum.

32. The composition according to claim 1 or 9, wherein said biological material is selected from the group consisting of ligaments, tendons, nerves, bone, teeth, bone marrow, skin grafts, cartilage, corneas, arteries, veins and organs for transplantation.

33. The composition according to claim 1 or 9, wherein said biological material is tissue.

34. The composition according to claim 33, wherein said tissue is selected from the group consisting of bone, grafts, joints, femurs, femoral heads, heart valves, ligaments, hearts, livers, lungs, kidneys, intestines, pancreas, limbs, digits and demineralized bone matrix.

35. The composition according to claim 1 or 9, wherein said biological material is bovine serum.

36. The composition according to claim 35, wherein said biological material is fetal bovine serum.

9. A composition comprising at least one biological material with residual solvent content, wherein the residual solvent content of said biological material is at a level effective to preserve said biological material for sterilization with radiation, wherein said biological material is glassy or vitrified.

10. The composition of claim 9, wherein said residual solvent content is less than 15%.

11. The composition of claim 9, wherein said residual solvent content is less than 10%.

12. The composition of claim 9, wherein said residual solvent content is less than 5%.

13. The composition of claim 9, wherein said residual solvent content is less than 2%.

14. The composition of claim 9, wherein said residual solvent content is less than 1%.

15. The composition of claim 9, wherein said residual solvent content is less than 0.5%.

16. The composition of claim 9, wherein said residual solvent content is less than 0.08%.

37. A method for sterilizing a biological material that is sensitive to radiation, said method comprising

adding to said biological material at least one stabilizer;

and

irradiating said biological material with radiation for a time effective to sterilize said biological material at a rate effective to sterilize and protect said biological material from said radiation, wherein said biological material is glassy or vitrified.

38. The method according to claim 37, wherein said at least one stabilizer is selected from the group consisting of polyhydric alcohols, DMSO and mixtures thereof.

39. The method according to claim 38, wherein said polyhydric alcohols are selected from the group consisting of trehalose, mannitol, glycerol and combinations thereof.

40. The method according to claim 37, wherein said at least one stabilizer comprises trehalose.

41. The method according to claim 37, wherein said at least one stabilizer comprises a polyhydric alcohol.

42. The method according to claim 37, wherein said at least one stabilizer comprises glycerol.

43. The method according to claim 37, wherein said at least one stabilizer comprises mannitol.

44. The method according to claim 37, wherein said at least one stabilizer comprises DMSO.

51. The method of claim 37 or 45, wherein said biological material is selected from the group consisting of monoclonal immunoglobulins, polyclonal immunoglobulins, glycosidases, sulfatases, urokinase and Factor VIII.

52. The method according to claim 37 or 45, wherein said biological material is selected from the group consisting of cells, tissues, blood, blood components, proteins, enzymes, immunoglobulins, botanicals, food, ligaments, tendons, nerves, bone, demineralized bone matrix, grafts, joints, femurs, femoral heads, teeth, skin grafts, bone marrow, heart valves, cartilage, corneas, arteries, veins, meat, organs, limbs, digits, lipids, carbohydrates, collagen, chitin, stem cells, islet of Langerhans cells, genetically altered cells, red blood cells, white blood cells, proteinaceous material and combinations thereof.

53. The method according to claim 52, wherein said blood components are selected from the group consisting of cellular blood components, blood proteins, liquid blood components and combinations thereof.

54. The method according to claim 52, wherein said collagen is selected from the group consisting of native collagen, afibrillar collagen, atelomeric collagen, soluble collagen and insoluble collagen.

55. The method according to claim 52, wherein said biological material comprises a protein or peptide produced from cell culture.

56. The method according to claim 37 or 45, wherein said biological material is whole or processed.

57. The method according to claim 37 or 45, wherein said biological material is selected from the group consisting of hearts, livers, lungs, kidneys, intestines and pancreas.

58. The method according to claim 37 or 45, wherein said biological material is human.

59. The method according to claim 37 or 45, wherein said biological material is mammalian.

60. The method according to claim 37 or 45, wherein said biological material is bovine.

61. The method according to claim 37 or 45, wherein said biological material is equine.

62. The method according to claim 37 or 45, wherein said biological material is porcine.

63. The method according to claim 37 or 45, wherein said biological material is transgenic or recombinant.

64. The method according to claim 63, wherein said biological material is milk.

65. The method according to claim 37 or 45, wherein said biological material is milk, collagen, plasma or serum.

66. The method according to claim 37 or 45, wherein said biological material is selected from the group consisting of ligaments, tendons, nerves, bone, teeth, bone marrow, skin grafts, cartilage, corneas, arteries, veins and organs for transplantation.

67. The method according to claim 37 or 45, wherein said biological material is tissue.

68. The method according to claim 67, wherein said tissue is selected from the group consisting of bone, grafts, joints, femurs, femoral heads, heart valves, ligaments, hearts, livers, lungs, kidneys, intestines, pancreas, limbs, digits and demineralized bone matrix.

69. The method according to claim 37 or 45, wherein said biological material is bovine serum.

70. The method according to claim 69, wherein said biological material is fetal bovine serum.

45. A method for sterilizing a biological material comprising residual solvent content, wherein said biological material is sensitive to radiation, said method comprising

reducing the residual solvent content of said biological material;

and

irradiating said biological material with radiation for a time effective to sterilize said biological material at a rate effective to sterilize and protect said biological material from said radiation,

wherein said residual solvent content of said biological material is reduced to a level effective to preserve said biological material and said biological material is glassy or vitrified.

46. The method of claim 45, wherein said residual solvent content is less than 5%.

47. The method of claim 45, wherein said residual solvent content is less than 2%.

48. The method of claim 45, wherein said residual solvent content is less than 1%.

49. The method of claim 45, wherein said residual solvent content is less than 0.5%.

50. The method of claim 45, wherein said residual solvent content is less than 0.08%.