Lyophilization apparatus and methods

• US 6,199,297 B1
• Filed: 02/01/1999
• Issued: 03/13/2001
• Est. Priority Date: 02/01/1999
• Status: Expired due to Term

• Current Assignee: Sartorius Stedim North America Inc. (Sartorius AG)
• Original Assignee: Integrated Biosystems, Inc. (Sartorius AG)
• Inventors: Wisniewski, Richard
• Primary Examiner(s): GRAVINI, STEPHEN MICHAEL
• Application Number:
  US09/241,745
• Time in Patent Office: 771 Days
• Field of Search: 342/84, 342/89, 34/92, 342/37, 342/42, 206/5, 206/6, 206/219, 206/220, 206/221, 206/439, 206/484.1, 206/524.8, 222/254, 222/256, 222/307, 222/311, 215/249, 215/251, 215/263, 215/264, 534/03, 534/32, 220/366.1, 220/367.1, 220/371, 220/373
• US Class Current: 34/284
• CPC Class Codes: B65D 51/241 provided with freeze-drying means
• CPC Class Codes: F26B 5/06 the process involving freezing

Abstract

Disclosed are bulk lyophilization containers including aseptic closure portions or heat flux equalization portions that promote improved bulk lyophilization. Also disclosed are methods of using the bulk lyophilization containers and improved lyophilization stoppers.

Claims

1. A bulk lyophilization container comprising:

a body portion; and

an aseptic closure portion,

wherein the body portion is coupled to the aseptic closure portion; and

the aseptic closure portion comprising an impervious membrane detachably coupled to the body portion via a membrane seal, wherein the impervious membrane may be detached from the body portion by tearing the membrane.

2. A bulk lyophilization container comprising;

a body portion;

an aseptic closure portion; and

at least two filling/ventilating necks;

wherein the body portion is detachably coupled to the aseptic closure portion, thereby facilitating removal of lyophilized product after lyophilization.

3. The bulk lyophilization container of claim 2, wherein the aseptic closure portion is detachably coupled to the body portion by at least one mechanical clamp.

4. A bulk lyophilization container comprising:

a body portion; and

an aseptic closure portion, wherein the body portion is coupled to the aseptic closure portion and the aseptic closure portion comprises a sealable neck, and the sealable neck capable of being sealed after lyophilization of a product contained in the bulk lyophilization container.

5. A bulk lyophilization container comprising:

a body portion; and

an aseptic closure portion, wherein the body portion is non-detachably coupled to the aseptic closure portion and wherein the bulk lyophilization container is stiff thereby improving lyophilization of a product contained in the bulk lyophilization container.

6. A bulk lyophilization container comprising:

a body portion;

an aseptic closure portion; and

at least one filling/ventilating neck, wherein the at least one filling/ventilating neck is mechanically reinforced to facilitate filling of a product or ventilation of vapors during lyophilization; and

wherein the body portion is coupled to the aseptic closure portion.

7. A bulk lyophilization container comprising:

a body portion;

an aseptic closure portion; and

at least one filling/ventilating neck; and

wherein the body portion is coupled to the aseptic closure portion, and the container is stiff thereby improving lyophilization of a product contained in the bulk lyophilization container.

8. A bulk lyophilization container comprising:

a body portion; and

an aseptic closure portion, wherein the body portion is coupled to the aseptic closure portion, and the bulk lyophilization container being stiff thereby improving lyophilization of a product contained in the bulk lyophilization container and the bulk lyophilization container possessing a geometric shape suitable for compact storage.

9. The bulk lyophilization container of claim 8, wherein the geometic shape includes a circular, triangular, elliptical, quadrilaterial, pentagonal, or hexagonal shape.

10. An array comprising bulk lyophilization containers, wherein the bulk lyophilization containers comprise:

a body portion; and

an aseptic closure portion;

wherein the body portion is coupled to the aseptic closure portion, and the bulk lyophilization container being stiff thereby improving lyophilization of a product contained in the bulk lyophilization container and the bulk lyophilization container possessing a geometric shape suitable for compact storage.

11. A method of storing lyophilized material, comprising:

storing the lyophilized material in bulk lyophilization containers;

wherein the bulk lyophilization containers comprise a body portion; and

an aseptic closure portion;

wherein the body portion is coupled to the aseptic closure portion, and the bulk lyophilization container being stiff thereby improving lyophilization of a product contained in the bulk lyophilization container and the bulk lyophilization container possessing a geometric shape suitable for compact storage.

12. A bulk lyophilization container comprising:

a body portion;

an aseptic closure portion; and

alignment or supporting aids coupled to the bulk lyophilization container;

wherein the body portion is coupled to the aseptic closure portion and the bulk lyophilization container being stiff thereby improving lyophilization of a product contained in the bulk lyophilization container.

13. The bulk lyophilization container of claim 12, wherein the alignment and support aids comprise edge support/alignment elements, support/alignment pins or raised center portions.

14. A bulk lyophilization container comprising:

a body portion;

an aseptic closure portion; and

optional liquid ports coupled to the bulk lyophilization container to facilitate addition or removal of liquid after lyophilization;

wherein the body portion is coupled to the aseptic closure portion.

15. A bulk lyophilization container comprising:

a body portion; and

an aseptic closure portion,

wherein the body portion is coupled to the aseptic closure portion via seals comprising seals formed by clamps and o-rings thereby facilitating removal of lyophilized product from the bulk lyophilization container following lyophilizaton.

16. A bulk lyophilization container comprising:

a body portion; and

an aseptic closure portion;

wherein the body portion is coupled to the aseptic closure portion via seals comprising seals formed by removable foil, thermoforming, heat sealing of polymers or heat sealing of multilayer materials, pressure-sensitive sealants, heat and compression techniques, or single-use seals.

17. The bulk lyophilization container of claim 16, wherein the single-use seals comprise a tack-welded seal, a notched wall seal, a notched corner seal, or a notched bottom seal.

18. A bulk lyophilization container comprising:

a body portion;

an aseptic closure portion; and

an edge sealing element coupled to tabs;

wherein the tabs and the edge sealing element define edge vents such that the edge vents provide a path for vapor to travel through during lyophilization, and wherein the aseptic closure portion and the body portion are coupled via the edge sealing element coupled to the tabs, and wherein the edge sealing element serves to form a seal between the aseptic closure portion and the body portion when the aseptic closure portion and the body portion are compressed together.

19. A bulk lyophilization container comprising:

a body portion;

an aseptic closure portion; and

a bi-lobe sealing element coupled to tabs;

wherein the tabs are designed to permit vapor flow to pass through or around the tabs during lyophilization, and wherein the aseptic closure portion and the body portion are coupled via the bi-lobe sealing element coupled to the tabs, and wherein the bi-lobe sealing element serves to form a seal between the aseptic closure portion and the body portion when the aseptic closure portion and the body portion are compressed together.

20. The bulk lyophilization container of claim 19, wherein the tabs extend towards an outer surface of the bulk lyophilization container.

21. The bulk lyophilization container of claim 20, wherein the tabs extend towards an inner surface of the bulk lyophilization container.

22. The bulk lyophilization container of claim 21, wherein the tabs are arranged such that they collapse between bi-lobes of the bi-lobe sealing elements.

23. A bulk lyophilization container comprising:

a flat body portion wherein the flat body portion facilitates removal of lyophilized product from the bulk lyophilization container following lyophilization; and

an aseptic closure portion;

wherein the body portion is coupled to the aseptic closure portion.

24. A bulk lyophilization container comprising:

a body portion; and

a flat aseptic closure portion wherein the flat aseptic closure portion facilitates removal of lyophilized product from the bulk lyophilization container following lyophilization;

wherein the body portion is coupled to the aseptic closure portion.