Method for filling pharmaceutical containers
In one general aspect, a method for filling multiple containers with a pharmaceutical product is disclosed, which comprises decontaminating sealed nested materials in a transfer chamber, removing from the sealed nested materials one or both of a container nest holding the multiple containers and a closure nest holding multiple closures, transferring from the transfer chamber to a controlled environment enclosure the removed nest, aseptically filling the containers with the pharmaceutical product, and closing the containers with the multiple closures. The nests are configured to allow multiple closures and containers to be simultaneously aligned concentrically, and closed simultaneously. Spring-loaded retaining structures on the closure nest allow it to releasably retain multiple closures above the corresponding multiple containers. In some embodiments the spring-loaded features are monolithically integrated with the closure nest. The product may be lyophilized in partially sealed containers while the sealing closures are releasably retained by the closure nest.
1. A method for aseptically filling a first plurality of containers with a pharmaceutical product in a first controlled environment enclosure, the method comprising:
providing first and second sealed nested materials, wherein the first sealed nested material comprises a container nest retaining a first plurality of containers, and the second nested material comprises a closure nest releasably retaining a plurality of closures;
decontaminating at least the first sealed nested material in a first transfer chamber;
placing the first transfer chamber in spatial communication with the first controlled environment enclosure;
aseptically gripping at least the decontaminated first sealed nested material;
transferring at least the gripped first sealed nested material into the first controlled environment enclosure;
removing the container nest from the decontaminated first sealed nested material within the first controlled environment enclosure;
removing the closure nest from the second sealed nested material;
filling the first plurality of containers with the pharmaceutical product in the first controlled environment enclosure; and
at least partially closing, in the first controlled environment enclosure, the filled first plurality of containers with the plurality of closures, wherein the container nest is vertically aligned and overlaid with the closure nest during the at least partially closing.
2. The method of claim 1 , wherein the aseptically gripping comprises manipulating a first articulated arm apparatus.
3. The method of claim 2 , wherein the filling comprises manipulating a second articulated arm apparatus.
4. The method of claim 1 , wherein the filling the first plurality of containers comprises filling simultaneously at least a portion of the first plurality of containers.
5. The method of claim 1 , wherein the filling the first plurality of containers with the pharmaceutical product comprises manipulating a first articulated arm apparatus to move at least one of the container nest and a fill needle system dispensing the pharmaceutical product.
6. The method of claim 5 , wherein the filling of the first plurality of containers with the pharmaceutical product comprises dispensing the pharmaceutical product from a fill needle.
7. The method of claim 5 , wherein the removing the container nest holding the first plurality of containers is by manipulating one of the first articulated arm apparatus and a second articulated arm apparatus.
8. The method of claim 5 , wherein the filling of the first plurality of containers with the pharmaceutical product comprises dispensing the pharmaceutical product simultaneously from a plurality of fill needles.
9. The method of claim 1 , wherein the at least partially closing the filled first plurality of containers comprises:
a. partially inserting the plurality of closures in the filled first plurality of containers so that each of the filled first plurality of containers is partially closed;
b. lyophilizing the pharmaceutical product in the first plurality of containers; and
c. sealing the first plurality of containers by exerting pressure on at least a portion of a plurality of caps associated with the plurality of closures.
10. The method of claim 9 , wherein the lyophilizing the pharmaceutical product comprises lyophilizing the pharmaceutical product in a stoppering apparatus having an interior that is one of isolated from the interior of the first controlled environment enclosure and in communication with the interior of the first controlled environment enclosure.
11. The method of claim 1 , wherein the partially closing the filled first plurality of containers comprises simultaneously partially closing at least a portion of the filled first plurality of containers.
12. The method of claim 1 , wherein the partially closing the filled first plurality of containers comprises partially closing all the filled first plurality of containers in the container nest simultaneously.
13. The method of claim 1 , wherein the partially closing the filled first plurality of containers comprises manipulating an articulated arm apparatus to place the filled first plurality of containers in a stoppering apparatus.
14. The method of claim 1 , further comprising returning the filled first plurality of containers to the first transfer chamber and terminating the spatial communication between the first transfer chamber and the first controlled environment enclosure.
15. The method of claim 1 , wherein the at least partially closing comprises completely closing and the method further comprises transferring the filled first plurality of containers to a second controlled environment enclosure.
16. The method of claim 1 , further comprising transferring the partially closed filled first plurality of containers to a second controlled environment enclosure.
17. The method of claim 1 , further comprising maintaining aseptic conditions in the first controlled environment enclosure.
18. The method of claim 1 , wherein the at least partially closing the filled first plurality of containers with the plurality of closures is at least partially closing the filled first plurality of containers while the first plurality of containers is in the closure nest.
19. The method of claim 1 , wherein the decontaminating includes at least one of electron beam decontamination and ultraviolet radiation decontamination.
20. The method of claim 1 , wherein the decontaminating includes at least one of steam and chemical exposure.
21. The method of claim 1 , wherein the decontaminating the first sealed nested material comprises covering the first sealed nested material with an impermeable cover.
22. The method of claim 1 , further comprising weighing the first plurality of containers while the first plurality of containers is in the container nest.
23. The method of claim 1 , wherein the aseptically gripping step includes aseptically gripping a tub of the first sealed nested materials.
24. The method of claim 1 , wherein the aseptically gripping step includes aseptically gripping a cover of the first sealed nested materials.
25. A method for aseptically filling a first plurality of containers with a pharmaceutical product in a first controlled environment enclosure, the method comprising:
providing first and second sealed nested materials, wherein the first sealed nested material comprises a container nest retaining a first plurality of containers, and the second nested material comprises a closure nest releasably retaining a plurality of closures;
decontaminating at least the second sealed nested material in a first transfer chamber;
placing the first transfer chamber in spatial communication with the first controlled environment enclosure;
aseptically gripping the decontaminated second sealed nested material;
transferring at least the gripped second sealed nested material into the first controlled environment enclosure;
removing the closure nest from the decontaminated second sealed nested material within the first controlled environment enclosure;
removing the container nest from the first sealed nested material;
filling the first plurality of containers with the pharmaceutical product in the first controlled environment enclosure; and
at least partially closing, in the first controlled environment enclosure, the filled first plurality of containers with the plurality of closures, wherein the closure nest is vertically aligned and overlaid with the container nest during the at least partially closing.
26. The method of claim 25 , wherein the aseptically gripping comprises manipulating a first articulated arm apparatus.
27. The method of claim 26 , wherein the filling comprises manipulating a second articulated arm apparatus.
28. The method of claim 25 , wherein the filling the first plurality of containers comprises filling simultaneously at least a portion of the first plurality of containers.
29. The method of claim 25 , wherein the filling the first plurality of containers with the pharmaceutical product comprises manipulating a first articulated arm apparatus to move one of the container nest and a fill needle system dispensing the pharmaceutical product.
30. The method of claim 29 , wherein the filling the first plurality of containers with the pharmaceutical product comprises dispensing the pharmaceutical product from a fill needle.
31. The method of claim 29 , wherein the filling the first plurality of containers with the pharmaceutical product comprises dispensing the pharmaceutical product simultaneously from a plurality of fill needles.
32. The method of claim 29 , wherein the removing the container nest holding the first plurality of containers is by manipulating one of the first articulated arm apparatus and a second articulated arm apparatus.
33. The method of claim 25 , wherein the at least partially closing the first plurality of containers comprises:
a. partially inserting the plurality of closures in the first plurality of containers;
b. lyophilizing the pharmaceutical product in the first plurality of containers; and
c. sealing the first plurality of containers by exerting pressure on at least a portion of a plurality of caps associated with the plurality of closures.
34. The method of claim 33 , wherein the lyophilizing the pharmaceutical product comprises lyophilizing the pharmaceutical product in a stoppering apparatus having an interior that is one of isolated from the interior of the first controlled environment enclosure and in communication with the interior of the first controlled environment enclosure.
35. The method of claim 25 , wherein the partially closing the first plurality of containers comprises simultaneously partially closing at least a portion of the first plurality of containers.
36. The method of claim 25 , wherein the partially closing the first plurality of containers comprises partially closing all the containers in the container nest simultaneously.
37. The method of claim 25 , wherein the closing the first plurality of containers comprises manipulating an articulated arm apparatus to place the first plurality of containers in a stoppering apparatus.
38. The method of claim 25 , further comprising returning the filled containers to the first transfer chamber and terminating the spatial communication between the first transfer chamber and the first controlled environment enclosure.
39. The method of claim 25 , wherein the at least partially closing comprises completely closing and the method further comprises transferring the filled containers to a second controlled environment enclosure.
40. The method of claim 25 , further comprising transferring the partially closed first plurality of containers to a second controlled environment enclosure.
41. The method of claim 25 , further comprising maintaining aseptic conditions in the first controlled environment enclosure.
42. The method of claim 25 , wherein the at least partially closing the first plurality of containers with the plurality of closures is at least partially closing the first plurality of containers while the first plurality of containers is in the closure nest.
43. The method of claim 25 , wherein the decontaminating is at least one of electron beam decontamination and ultraviolet radiation decontamination.
44. The method of claim 25 , wherein the decontaminating is by means of at least one of steam and chemical exposure.
45. The method of claim 25 , wherein the decontaminating the second sealed nested material comprises covering the second sealed nested material with an impermeable cover.
46. The method of claim 25 , further comprising weighing the first plurality of containers while the first plurality of containers is in the container nest.
47. The method of claim 25 , wherein the aseptically gripping step includes aseptically gripping a tub of the second sealed nested material.
48. The method of claim 25 , wherein the aseptically gripping step includes aseptically gripping a cover of the first sealed nested material.