U.S. patent application number 10/532404 was filed with the patent office on 2006-03-09 for systems, devices and methods for aseptic processing.
Invention is credited to William Merrill, ThomasL Thorpe.
Application Number | 20060048844 10/532404 |
Document ID | / |
Family ID | 32176615 |
Filed Date | 2006-03-09 |
United States Patent
Application |
20060048844 |
Kind Code |
A1 |
Merrill; William ; et
al. |
March 9, 2006 |
Systems, devices and methods for aseptic processing
Abstract
Certain exemplary embodiments can provide a system comprising an
automatic container positioner that, in an operative embodiment,
positions a container for introduction of a filling to the
container via a filling inlet of the container. In certain
embodiments, the container can be located in a critical zone
positioned in an airflow encountering no Class 100 contaminant
generators upstream from the critical zone. In certain embodiments,
the positioner can be located downstream of the filling inlet of
the container.
Inventors: |
Merrill; William; (Afton,
VA) ; Thorpe; ThomasL; (Chalottesville, VA) |
Correspondence
Address: |
MICHAEL N. HAYNES
1341 HUNTERSFIELD CLOSE
KESWICK
VA
22947
US
|
Family ID: |
32176615 |
Appl. No.: |
10/532404 |
Filed: |
October 22, 2003 |
PCT Filed: |
October 22, 2003 |
PCT NO: |
PCT/US03/33689 |
371 Date: |
April 22, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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60420691 |
Oct 23, 2002 |
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Current U.S.
Class: |
141/85 |
Current CPC
Class: |
A61L 9/00 20130101; B65B
3/003 20130101; B65B 31/027 20130101; B65B 55/12 20130101 |
Class at
Publication: |
141/085 |
International
Class: |
B65B 1/04 20060101
B65B001/04 |
Claims
1. A method comprising a plurality of activities comprising: via a
system comprising an autoclaveable automatic
non-electrically-driven container positioner, automatically
transporting a container within a critical zone located in an
airflow that encounters no Class 100 contaminant generators
upstream from the critical zone, the container positioner located
downstream from a filling inlet of the container; and automatically
introducing a filling to the container via the filling inlet of the
container.
2. The method of claim 1, further comprising: preloading the
container into the system.
3. The method of claim 1, further comprising: providing the
container to the container positioner.
4. The method of claim 1, further comprising: preloading a closure
into the system.
5. The method of claim 1, further comprising: shielding the
container from contamination.
6. The method of claim 1, further comprising: shielding the
container from contamination when outside the critical zone.
7. The method of claim 1, further comprising: shielding a closure
from contamination.
8. The method of claim 1, further comprising: shielding a closure
from contamination when outside the critical zone.
9. The method of claim 1, further comprising: providing a closure
to the container.
10. The method of claim 1, further comprising: positioning a
closure on the container.
11. The method of claim 1, further comprising: positioning a
closure on the container while the container is within the critical
zone.
12. The method of claim 1, further comprising: automatically
positioning a closure on the container.
13. The method of claim 1, further comprising: closing the
container.
14. The method of claim 1, further comprising: securing a closure
on the container.
15. The method of claim 1, further comprising: crimping a closure
onto the container.
16. The method of claim 1, further comprising: crimping a closure
onto the container when the container is outside the critical
zone.
17. The method of claim 1, further comprising: automatically
crimping a closure onto the container.
18. The method of claim 1, wherein the container is sterile.
19. The method of claim 1, wherein the container remains covered
until entry into the critical zone.
20. The method of claim 1, wherein the container remains sterile
until said introducing activity.
21. The method of claim 1, wherein a closure for the container is
sterile.
22. The method of claim 1, wherein a closure for the container
remains sterile until placed in contact with the container.
23. The method of claim 1, wherein the container positioner is
driven pneumatically.
24. The method of claim 1, wherein during normal operation, the
container is isolated from a human operator of the system.
25. The method of claim 1, wherein during normal operation, the
container is isolated from contaminants.
26. The method of claim 1, wherein the system weighs less than
about 300 pounds.
27. The method of claim 1, wherein the container positioner weighs
less than about 60 pounds.
28. The method of claim 1, wherein components of the system are
manually assembleable to form an operative embodiment of the
system.
29. The method of claim 1, wherein components of the system are
manually assembleable without tools to form an operative embodiment
of the system.
30. The method of claim 1, wherein the system is adapted to be
contained within a standard laboratory hood.
31. The method of claim 1, wherein no components of the system are
located downstream from the container positioner.
32. The method of claim 1, wherein no moving components of the
system are located downstream from the container positioner.
33. A system comprising: an autoclaveable automatic
non-electrically-driven container positioner that, in an operative
embodiment, positions a container for introduction of a filling to
the container via a filling inlet of the container, the container
located in a critical zone positioned in an airflow encountering no
Class 100 contaminant generators upstream from the critical zone,
said container positioner located downstream of the filling inlet
of the container.
34. The system of claim 33, further comprising a container storage
subassembly.
35. The system of claim 33, further comprising a container storage
subassembly adapted to provide a container to said container
positioner.
36. The system of claim 33, further comprising a container storage
subassembly adapted to receive a container from said container
positioner.
37. The system of claim 33, further comprising an automatic filling
subsystem for introducing the filling to the container.
38. The system of claim 33, further comprising an automatic and
intermittent filling subsystem for introducing the filling to the
container, said filling subsystem comprising a manually removable
filling needle coupled via a disposable tubing to a pumping
device.
39. The system of claim 33, further comprising a closure storage
subassembly.
40. The system of claim 33, further comprising a closure storage
subassembly adapted to provide a closure to a closure positioning
subassembly.
41. The system of claim 33, further comprising a closure
positioning subassembly.
42. The system of claim 33, further comprising a fluidically-driven
closure positioning subassembly.
43. The system of claim 33, further comprising a closure
positioning subassembly adapted to position a closure over the
container.
44. The system of claim 33, further comprising a closure
positioning subassembly adapted to position a closure on the
container.
45. The system of claim 33, further comprising a closure
positioning subassembly adapted to position a closure in the
container.
46. The system of claim 33, further comprising a closing
subassembly adapted to secure a closure to the container.
47. The system of claim 33, further comprising a fluidically-driven
closing subassembly adapted to secure a closure to the
container.
48. The system of claim 33, wherein said container positioner is
adapted to position a container in a fill location.
49. The system of claim 33, wherein said container positioner is
adapted to position a container in a fill location located in the
critical zone.
50. The system of claim 33, wherein said container positioner is
adapted to advance a container after introduction of the filling
into the container.
51. The system of claim 33, wherein said container positioner is
adapted to advance a container through the critical zone.
52. The system of claim 33, wherein said container positioner is
adapted to remove a container from a fill location.
53. The system of claim 33, wherein said container positioner is
pneumatically driven.
54. The system of claim 33, wherein said system comprises no hinges
upstream in the airflow from the critical zone.
55. The system of claim 33, wherein the container is shielded from
contamination before entering the critical zone.
56. The system of claim 33, wherein the container is shielded from
contamination after leaving the critical zone.
57. The system of claim 33, wherein the container is shielded from
contamination when outside the critical zone.
58. The system of claim 33, wherein said system comprises no gears
located upstream in the airflow from the critical zone.
59. The system of claim 33, wherein said system is portable.
60. The system of claim 33, wherein said system is
decontaminateable.
61. The system of claim 33, wherein said system is
decontaminateable in an operable embodiment prior to operation.
62. The system of claim 33, wherein said system is
decontaminateable in an operable embodiment after operation.
63. The system of claim 33, wherein said system is
decontaminateable without the use of chemical disinfectants.
64. The system of claim 33, wherein the system is manually
introduceable to an autoclave.
65. The system of claim 33, wherein said system conforms to an FDA
document entitled "Guideline on Sterile Drug Products Produced by
Aseptic Processing" published June 1987.
66. The system of claim 33, wherein said system conforms to an FDA
document entitled "Guidance for Industry, Sterile Drug Products
Produced by Aseptic Processing--Current Good Manufacturing
Practice" (Draft--August 2003).
67. The system of claim 33, wherein during normal operation, said
system is isolated from a human operator of said system.
68. The system of claim 33, wherein during normal operation, said
system is isolated from contaminants.
69. The system of claim 33, wherein during normal operation, said
system is shielded from contaminant entry into critical zone
perpendicularly to the airflow.
70. The system of claim 33, wherein said system weighs less than
about 300 pounds.
71. The system of claim 33, wherein said system is manually
assembleable to form an operative embodiment of said system.
72. The system of claim 33, wherein said system is manually
assembleable without tools to form an operative embodiment of said
system.
73. The system of claim 33, wherein said system is adapted to be
contained within a standard laboratory hood.
74. The system of claim 33, wherein during normal operation, said
system is incapable of breaking the container.
75. The system of claim 33, wherein during normal operation, said
system is incapable of crushing the container.
76. The system of claim 33, wherein during normal operation, no
components of said system are located downstream in the airflow
from the critical zone.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to and incorporates by
reference herein in its entirety, pending U.S. Provisional Patent
Application Ser. No. 60/420,691 (Applicant Docket No. 00100-01),
titled "Aseptic Liquid Filler Apparatus and Related Method
Thereof", filed 23 Oct. 2003.
BRIEF DESCRIPTION OF THE DRAWINGS
[0002] A wide array of potential embodiments can be better
understood through the following detailed description and the
accompanying drawings in which:
[0003] FIG. 1 is a block diagram of an exemplary embodiment of
system 1000;
[0004] FIG. 2 is a top view of an exemplary embodiment of system
2000;
[0005] FIG. 3 is a front view of an exemplary embodiment of a
container positioning system 3000;
[0006] FIG. 4 is a block diagram of an exemplary embodiment of an
information device 4000;
[0007] FIG. 5 is a flow chart of an exemplary embodiment of a
method 5000;
[0008] FIG. 6 is a top view of an exemplary embodiment of a
container positioning system 6000;
[0009] FIG. 7 is a front view of an exemplary embodiment of a
Rivard shuttle 6100;
[0010] FIG. 8 is a top view of an exemplary embodiment of a
stationary rail 6300;
[0011] FIG. 9 is a top view of an exemplary embodiment of a
guardrail 6400; and
[0012] FIG. 10 is a top view of an exemplary embodiment of a rod
6200.
Definitions
[0013] When the following terms are used herein, the accompanying
definitions apply: [0014] airflow--a substantially unidirectional
current of gas that is substantially aimed at the critical zone
during operation. An airflow can comprise an inert gas, such as
nitrogen, argon, etc., filtered air, such as HEPA filtered air,
etc. An airflow can be substantially linear, substantially laminar,
and/or without substantial turbulence. [0015] aseptic--free of or
using methods to keep free of pathological microorganisms; sterile.
[0016] autoclaveable--capable of functioning normally, and designed
to function normally, after sterilization via a moist heat
autoclave. [0017] clean--devoid of contaminants. For example, a
clean container can be devoid of chemical and/or biological
contaminants that might jeopardize the efficacy and/or safety of a
filling to be stored therein. [0018] closure--a device for
enclosing an opening of a container or for securing another
closure. Examples of a closure include a stopper, syringe plug,
cap, metallic overlay cap for a stopper, etc. [0019] container--an
enclosure for a filling having a closable opening via which the
filling can be introduced. Examples of a container include a vial,
syringe, bottle, etc. [0020] container positioner--a device for
imparting directionally and temporally controlled motion to
containers to transport the containers to, through, and/or from one
or more processing stations. [0021] contaminant--an undesired
chemical and/or biological material. Examples include particulates,
microbes, bacteria, viruses, mold spores, disinfectant residue,
etc. Contaminants can be airborne or residing on a surface. [0022]
contaminant generator--a source of greater than a predetermined
number of contaminant particles and/or droplets per cubic meter in
a size range of about 0.3 micron and larger to about 0.5 micron and
larger when counted at representative locations not more than 1
foot away from the critical zone, within the airflow, during
filling or closing operations. For a Class 100 (ISO 5, per ISO
14644-1) contaminant generator, the predetermined number of
contaminants is 3520. For a Class 1000 contaminant generator, the
predetermined number is 35,200. For a Class 10,000 contaminant
generator, the predetermined number is 352,000. For a Class 100,000
contaminant generator, the predetermined number is 3,520,000.
Examples include mechanical, hydraulic, pneumatic, and/or
electrical parts, stored containers, and/or stored closures that
experience friction (e.g., rub, slide, grind, abrade, and/or wear),
vibration, leakage, and/or condensation, thereby generating at
least microscopic particles and/or droplets therefrom. Other
examples include unfiltered air sources that can enter the critical
zone during operation; human operators that, during operation, can
shed skin cells, fibers, dust, etc., exhale droplets of saliva
and/or mucus, etc.; structural supports and/or machine components
below the critical zone that can substantially impede the airflow,
cause substantial turbulence in the airflow, and/or harbor and
release contaminants and/or spilled filling. A Class 100
contaminant generator can provide more than one colony forming unit
per 10 cubic feet of air from the airflow. [0023] critical zone--a
volume within which, during operation, a container is directly
exposed to the airflow, and which is defined by an entry position
of the container into, and an exit position of the container from,
one or more processing locations at which (1) a filling is
introduced to the container via a filling opening, and (2) the
filling opening is at least partially covered by a closure, and all
positions of the container therebetween the entry and exit
positions. [0024] decontaminateable--capable of being
decontaminated without the use of chemical disinfectants and via
insertion into a washer or sterilizer (e.g., moist heat, dry heat,
gas, radiation, etc.) to meet a predetermined standard prior to or
subsequent to operation. For example, a system and/or device can be
decontaminateable to meet the FDA's "Industry Guideline on Sterile
Drug Products Produced by Aseptic Processing" (June 1987), the
FDA's "Guidance for Industry, Sterile Drug Products Produced by
Aseptic Processing--Current Good Manufacturing Practice"
(Draft--August 2003), 21 CFR parts 210 and 211, and/or 21 CFR parts
600 through 680, all of which are incorporated by reference herein
in their entirety. A decontaminateable filling system can, for
example, fit within a standard laboratory hood, manually portable
by a single human of average strength, evacuable, autoclaveable,
and/or moist heat sterilizable. [0025] fill--to introduce a filling
to a container during operation. A container need not be completely
filled. [0026] filling--an intended content of a container
subsequent to a fill operation. A filling can be a pharmaceutical,
parenterals, biological, growth media, medicament, chemical,
radioactive, cosmetic, food product, beverage, powder, solid,
liquid, slurry, gas, vapor, mixture, etc. A filling is generally
not intended to comprise a contaminant. [0027]
non-electrically-driven--driven by other than an electrical motor
or other electrical device. For example, driven by a fluidic;
hydraulic, pneumatic, and/or magnetic system, device, and/or power
source, which itself could be driven by an electrical device.
[0028] particulate--contaminant particles, typically generated
during operation. Examples include particles generated and/or
provided by a mechanical, hydraulic, pneumatic, and/or electrical
machine component, human operator, unfiltered air source, etc.
[0029] shield--when used as a verb, to prevent direct impingement
by the airflow and/or airborne contaminants during operation.
[0030] sterile--devoid of living biological contamination; a subset
of clean. [0031] upstream--between a source of the airflow and the
critical zone. The source can be, for example, a hood, a duct, an
outlet, a diffuser, and/or a filter, etc. that directs the airflow
at the critical zone. Publications
[0032] The following U.S. Patents are hereby incorporated by
reference herein in their entirety: TABLE-US-00001 6,385,943 Yuyama
et al. 6,308,494 Yuyama et al. 6,115,996, Yuyama et al. 5,946,883
Yuyama et al. 5,979,515 Olsson 5,765,342 Jensen et al. 5,678,393
Yuyama et al. 5,673,535 Jagger RE37,471 Jagger RE37,829 Charhut et
al. 5,746,042 Lombardi 5,798,020 Coughlin et al.
DETAILED DESCRIPTION
[0033] Many pharmaceuticals are injected directly into the
patient's body. While this method can quickly expose the body to
the drug, it also can subject the body to any contaminants found
within the drug container. Manufacturers of injectable drugs
(parenterals) can strive for assurance of the sterility and purity
of these products. Specific contaminates can include surface and
air borne microbes, particulates, and residue from prior uses
and/or cleanings.
[0034] A parenteral drug can be rendered sterile by: 1) terminal
sterilization, and/or 2) filter sterilization followed by aseptic
filling. Terminally sterilizing a parenteral drug after filling
into its final container is similar to canning food. The container
is subjected to high heat to sterilize its sealed contents. When
the parenteral drug (usually bio-pharmaceuticals or biologic-based
drugs) cannot withstand the high temperatures, the drug can be
filter-sterilized prior to aseptic filling into its final
container. Because there is no terminal sterilization, any
recontamination of the parenteral drug during filling will likely
remain with the drug.
[0035] Guidelines for aseptic processing of parenteral drugs are
provided in the Federal Food and Drug Administration's (FDA)
"Guideline on Sterile Drug Products Produced by Aseptic Processing"
(June 1987) and/or the FDA's "Guidance for Industry, Sterile Drug
Products Produced by Aseptic Processing--Current Good Manufacturing
Practice" (Draft--August 2003), both of which are incorporated by
reference herein in their entirety.
[0036] To meet and/or exceed these guidelines, the drug and/or the
components (containers, closures, and/or filling lines, etc.) that
come in contact with the drug can be cleaned, sterilized, and
protected. In addition, equipment surfaces in the vicinity of the
product and the product contact components can be decontaminated.
Sterile, particulate-free, laminar air (HEPA) can be flushed (e.g.,
down from above, up from below, horizontally, and/or diagonally,
etc.) upon these surfaces to cleanse the area. The sterile air can
have a velocity of from about 50 to about 150 feet per minute,
including all values and subranges therebetween, such as from about
70 to about 110 fpm, etc. Operators can be gowned in sterile
garments and trained to minimize contact with these critical areas.
Threats to this environment can include inadequately decontaminated
and disinfected equipment, particulate generation by the equipment,
and/or mishaps in the filling process that spread contamination or
require excessive intervention by an operator.
[0037] FIG. 1 is a block diagram of an exemplary embodiment of a
container filler system 1000, which can comprise any of various
components, subsystems, and/or subassemblies. For example,
container filler system 1000 can comprise a container supplier
and/or container supply subsystem and/or subassembly 1100 that
provides containers to a base unit and/or container filler and/or
container filling subsystem 1200. Once filled, a closure supplier
and/or closure supply subsystem 1300 can provide a closure that can
be used to close the container. Once filled and closed, the
containers can be provided to a container packaging subsystem 1400.
Filtered air can be provided to the container filling subsystem
1200 by a filtered gas subsystem 1500 (e.g., air, nitrogen, oxygen,
etc.). A filling can be provided to the containers by a filling
pumping system 1600. A non-electrical power subsystem 1800 can
operate at least a portion of container filling subsystem 1200. A
programmable control system 1700, which can comprise an information
device, such as for example a programmable logic controller (PLC),
can control any of container supply subsystem 1100, container
filling subsystem 1200, closure supply subsystem 1300, container
packaging subsystem 1400, filtered air subsystem 1500, filling
pumping system 1600, power subsystem 1800. Container supply
subsystem 1100, container filling subsystem 1200, and/or closure
supply subsystem 1300 can be positioned in an operating zone
1800.
[0038] Certain exemplary embodiments of system 1000 can have
utility for filling containers with pharmaceuticals, biologicals,
growth media, food products, cosmetics, flavorings, essences,
clinical fills, bio-hazardous materials, and/or cytotoxic
materials. Certain exemplary embodiments can be useful to handlers
of chemical and/or nuclear materials.
[0039] In certain exemplary embodiments, container supply subsystem
and/or closure supply subsystem 1300 can be integral to container
filling subsystem 1200. In certain exemplary embodiments, container
filling subsystem 1200 can be implemented as a bench-top apparatus
that can be relatively easily disassembled, decontaminated,
sterilized, and/or reassembled and can preserve the purity and/or
sterility of a liquid drug product.
[0040] Certain exemplary embodiments of container filling subsystem
1200 can be suitable for an open class 100 clean room, a biohazard
hood, and/or an isolator glove-box. Certain exemplary embodiments
of container filling subsystem 1200 can be relatively small (e.g.,
about 18'' deep by about 28'' wide by about 48'' tall, but not
limited thereto). Certain exemplary embodiments of container
filling subsystem 1200 can weigh less than from about 10 pounds to
about 300 pounds (including all values therein, such as about 20,
30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 200, and/or 250 pounds,
etc., and subranges therein, such as from about 25 to about 45
pounds, from about 30 to about 55 pounds, etc.). Certain exemplary
embodiments of container filling subsystem 1200 can be manually
disassembleable, manually transportable, manually loadable in an
autoclave, and/or manually assembleable. Certain exemplary
embodiments of container filling subsystem 1200 can be
pneumatically-operated. Certain exemplary embodiments of container
filling subsystem 1200 can include a clear shield to shelter the
container path, filling zone, closing zone, and/or critical zone
from the mechanical parts. The mechanical parts can be designed to
avoid particulate generating and/or microbial-harboring elements.
To further protect the product and/or product components, certain
exemplary embodiments can have no hinged and/or particulate
generating parts and/or contaminant generators in, above, below,
upstream, and/or downstream of, the critical zone.
[0041] In certain exemplary embodiments, container filling
subsystem 1200 can be placed in a washer to decontaminate and then
inserted in an autoclave. This can generate considerably greater
assurance than hand wiping and rinsing that container filling
subsystem 1200 is decontaminated and sterile, without the potential
introduction chemical disinfectant residues. Container filling
subsystem 1200 can then be moved under a laminar airflow hood or
filter and unwrapped.
[0042] Containers can be preloaded in container supply subsystem
1100, which can holds from about 1 to about 1000 containers,
including all values and subranges therebetween. Container supply
subsystem 1100 can be a carousel, vibrating bowl, and/or hopper,
etc. If implemented as a carousel, the containers can be preloaded
as vertical strips, encased under a "cake lid" type shield, and
sterilized.
[0043] Similarly, closures also can be preloaded in a closure
supply subsystem 1300, which can hold from about 1 to about 1000
closures, including all values and subranges therebetween. Closure
supply subsystem 1300 can be a carousel, vibrating bowl, and/or
hopper, etc. If implemented as a carousel, the closures can be
preloaded as vertical strips, encased under a "cake lid" type
shield, and sterilized. In certain exemplary embodiments, both the
container and the closure carousels can be attached and/or
attachable to the base unit. Both the containers and the closures
can remain protected under the cake covers, thereby potentially
avoiding exposure to the operator and/or to environmental
contaminates. The containers and closures can index down and can be
deposited to the point of use, remaining covered until about their
moment of use.
[0044] Certain exemplary embodiments of subsystem 1200 allow the
containers to be supported by a rail having a number of holes
therethrough to decrease the resistance of the rail to the airflow
impinging on the rail. For example, from about 0 to about 75
percent of the projected surface area of the rail perpendicular to
the airflow can be perforated. As another example, the rail can
comprise one or more horizontal round bars upon which the
containers are vertically supported. As yet another example, the
rail can be one or more vertically-oriented knife-edges upon which
the containers are vertically supported. As still another example,
in an airflow that is directed vertically upwards, the containers
can be levitated by the airflow, such that no rail is needed to
provide vertical support to the containers. In any event, the rail
can be designed to minimize aerodynamic drag, minimize projected
surface area that is perpendicular to the airflow, and/or provide a
surface and/or medium upon which the container can glide and/or be
slid by the container positioner. The containers can intermittently
and/or continuously travel along the rail, above the floor, and/or
with nothing located between the rail and the floor. That is, no
mechanical parts, motors, or pneumatic components need be located
under the critical zone and/or rail. Such embodiments can allow
full laminar airflow through the critical zone to keep this zone
flushed with clean air. Also, such embodiments can allow spills to
drop to the floor, thereby reducing and/or eliminating equipment
contamination and/or facilitating cleanup.
[0045] In certain exemplary embodiments, the filling can be a
solution that is moved by a pump into the container via a
disposable tube connected to a disposable filling needle. Because
most pumps can not be adequately decontaminated and/or autoclaved,
filling pumping system 1600, and/or a component pump thereof, can
be located outside the critical zone, the operation zone 1900,
and/or the clean room (if utilized). Although a wide range of pumps
can be used with filling pumping system 1600, certain exemplary
embodiments utilize a peristaltic pumping unit manufactured by
Masterflex, a division of the Barnant Company (Barrington, Ill.).
Multiple filling needles and/or stations are possible.
[0046] In certain exemplary embodiments, closure supply subsystem
1300 can supply a closure to subsystem 1200 and/or to a container.
In certain exemplary embodiments, closure supply subsystem 1300
and/or each closure can be located outside of the critical zone
and/or the airflow upstream of the critical zone except during
provision to a container. That is, only the closure and the device
providing the closure to the container (a closure provider,
applier, and/or inserter) need enter the airflow upstream of the
critical zone. Such a closure provider, applier, and/or inserter
(which can be comprised by subsystem 1200) can, for example, pick
up a closure via vacuum outside the airflow upstream of the
critical zone, protrude through a protective shield, affix the
closure to the container, and then retract. In various embodiments,
the closure provider, applier, and/or inserter and the closure can
protrude through the shield and be in place prior to the container
being in position for affixing of the closure, or the provider,
applier, and/or inserter and closure can protrude through the
shield during or after positioning of the container for affixing of
the closure.
[0047] Multiple closure supply subsystems 1300 are possible. For
example, a first closure supply subsystem can provide, apply,
and/or insert a first closure, such as a stopper, lid, and/or cap,
etc., to a container, and a second closure supply subsystem can
provide and/or apply a metallic overlay to the first closure.
[0048] In certain exemplary embodiments, container supply subsystem
1100, container filling subsystem 1200, and/or closure supply
subsystem 1300 can be operated and/or driven non-electrically by
power subsystem 1700, which can comprise a fluidic, hydraulic,
pneumatic, and/or magnetic power source. For example, operation of
a subsystem 1100, 1200, and/or 1300 can be fully pneumatic to avoid
heat generation from electric motors and allow the subsystem to be
fully washed and sterilized. Moreover, pneumatic operation can
enable the subsystem to be normally operated at a sufficiently low
pressure to avoid damaging, breaking, and/or crushing one or more
containers (the unit can just stall) and/or risk operator injury
from moving parts.
[0049] When operations are complete, system 1000 can be partially
dismantled into its constituent subsystems and certain of those
subsystems, such as for example container supply subsystem 1100,
container filling subsystem 1200, and/or closure supply subsystem
(but probably not container packaging subsystem 1400, filtered air
subsystem 1500, filling pumping system 1600, programmable control
system 1700, and/or power subsystem 1800), can be put in a washer
and/or autoclaved (steam sterilized).
[0050] Certain exemplary embodiments of system 1000 and/or one or
more of its subsystems can allow for any of the following: [0051]
compliance with the FDA "Guideline on Sterile Drug Products
Produced by Aseptic Processing" (June 1987) and/or the FDA
"Guidance for Industry, Sterile Drug Products Produced by Aseptic
Processing--Current Good Manufacturing Practice" (Draft--August
2003); [0052] preloading of containers--relatively little to no
direct operator contact after sterilization; [0053] preloading of
closures--relatively little to no direct operator contact after
sterilization; [0054] covered containers and/or
closures--relatively little to no environmental exposure to
contaminants; [0055] a shielded critical zone--shielding can
substantially shield open containers from environmental exposure to
contaminants; [0056] open bottom--can allow laminar air flow
through at least container filling subsystem 1200; [0057] open
bottom--can allow product fall through to avoid collateral
contamination; [0058] no tool setup--use of pegs can allow
relatively fast set-up and can minimize contamination from operator
and/or environmental sources; [0059] few parts--relatively quick
and/or easy setup, decontamination, and/or sterilization; [0060]
pneumatic drives--autoclaveable and/or can potentially reduce
and/or eliminate container breakage, and thereby potentially reduce
and/or eliminate broken glass and the potential contamination
and/or safety issues associated therewith, and/or an unwanted spray
or dripping of filling; [0061] conveyor--Rivard shuttle can be
relatively clean, simple, open architecture, and/or easy to
decontaminate and/or sterilize; [0062] closure insertion
unit--mechanism located substantially outside the airflow directed
at the critical zone; [0063] no hinges or gears in critical zone or
airflow upstream of the critical zone--helps minimize
contamination, decontamination, and/or sterilization issues; [0064]
relatively open architecture of system 1000 and/or container
filling subsystem 1200 can help avoid disruption of, and/or
preserve, the substantially linear and/or laminar velocity and/or
direction of the clean airflow upstream of, throughout, and/or
below the critical zone.
[0065] FIG. 2 is a top view of an exemplary embodiment of a system
2000, which can comprise a container supply subsystem 2100, a
container supply chute 2150, a critical zone 2200, an operation
zone 2250, container positioner and/or container positioning
subsystem and/or container transport and/or container transport
subsystem 2300, an exterior shield 2420, and interior shield 2440,
a container fill nozzle 2460, a first closure storage 2500, a first
closure provider/applier/inserter 2540, second closure storage
2600, a second closure provider/applier/inserter 2640, a filled
container discharge chute 2700, and/or a frame 2800, etc.
[0066] Various components of system 2000 can be supported by a
frame 2800, which can provide a relatively open architecture that
can allow the airflow through and/or adjacent critical zone 2200 to
sweep particles away from the open containers. The minimization of
horizontal surfaces in frame 2800 also can facilitate the
decontamination of system 2000 by eliminating many surfaces on
which contaminants and/or spilled filling can accumulate. In
certain exemplary embodiments, few or no electrical and/or
mechanical devices are attached and/or present beneath a top
portion of frame 2800.
[0067] In certain exemplary embodiments, frame 2800 can comprise
welded one-inch, square stainless steel tubing, such as type 316L
if the frame will be steam sterilized. Other materials of suitable
strength and rigidity may be substituted. The general outside
dimensions of frame 2800 can be about 26 inches wide by about 18
inches deep by about 6 inches high. Other dimensions and materials
may be selected.
[0068] Positionable, supportable, and/or mountable on frame 2800
can be a container supply subsystem 2100, which can store, protect,
and/or deliver containers. Any of many potential embodiments for
container supply subsystem 2100 can be utilized, such as for
example, a container carousel, hopper, bowl feeder, and/or
conveyor, etc. Container supply subsystem 2100 can be preloaded and
covered prior to sterilization, thereby protecting the containers
from handing and environmental contaminates.
[0069] In certain exemplary embodiments, container supply subsystem
2100 can be implemented as a container carousel. One method of
building a container carousel is using two pieces, a rack and a
cover (not shown). The carousel can hold between about 1 and about
1000 containers (including all values and subranges therebetween)
that can range in volume from about 1 ml to about 100 ml (including
all values and subranges therebetween). The empty containers can be
pre-loaded onto the carousel, with their longitudinal axis oriented
horizontally and with their open ends facing outward, and the
entire carousel covered prior to sterilization. If constructed of
appropriate materials, the carousel can be dry heat sterilized to
over 250 degrees C. or moist heat sterilized to about 121 degrees
C. Once sterilized, the carousel can be placed onto a container
carousel plate of system 2000.
[0070] The container carousel can be formed of welded 16-gage
stainless steel sheet, preferably type 316L if the carousel will be
steam sterilized. Other materials of suitable strength and rigidity
may be substituted. The carousel can be ringed with vertical slots
that can hold empty containers. The base of the carousel can be a
solid disk with the exception of one portal that can allow the
containers to drop through. After a vertical row has emptied of
containers, the carousel can index to move a full vertical row of
containers over the open portal. The containers can promptly drop
through the portal and into a container chute 2150.
[0071] In an exemplary embodiment, for a 1 inch diameter.times.2
inch high 10 ml glass vial with a 20 mm opening, the outside
carousel dimensions can be about 10 inch diameter.times.10 inches
high. This carousel can have 25 vertical slots, each holding 6
vials and thereby can hold a total of 150 vials. One additional,
empty or blank slot can be included to enable the carousel to be
transported without vials dropping through the portal. Other sizes
and modifications are possible.
[0072] Container chute 2150 can reorient (if necessary) containers
arriving from the container supply subsystem 2100. Container chute
2150 can also protect the open containers from handling and
contaminants. Container chute 2150 can be installed onto frame 2800
prior to sterilization of frame 2800. Container chute 2150 can be
in place prior to the attachment of container supply subsystem
2100.
[0073] Container chute 2150 can be shaped to accommodate each size
of container used. Container chute 2150 can be manufactured of
solid or welded stainless steel, such as type 316L, if container
chute 2150 will be steam sterilized. Other materials of suitable
strength and rigidity may be substituted.
[0074] Container chute 2150 can present the containers to a
container transport subsystem 2300 that transports the containers
through a critical zone 2200 within which the containers can be
filled and/or at least partially closed while an interior of the
container is directly exposed to the airflow.
[0075] Container positioner and/or container transport subsystem
2300 can transport containers to, through, and/or from a series of
various processing stations, such as a container entry position
2330, a container fill position 2340, a container first closure
affixing position 2350, a container dwell position 2360, a
container second closure affixing position 2370, and/or a container
exit position 2380, etc.
[0076] Among the many other potential stations (not shown) include
stations for weighing, gas purging, closure providing, closure
applying, closure inserting, overcapping, container diverting,
lyophilization, filler inspection, head-space inspection, machine
vision inspection, and/or labeling, etc. Upon exiting container
transport subsystem 2300, a container can enter a container
discharge chute 2700, which can lead to a filled container storage
subsystem, a filled container lyophilization subsystem, and/or a
filled container packaging subsystem, etc.
[0077] Container transport subsystem 2300 can impart directionally
and temporally controlled motion to the containers via any of a
wide variety of devices, such as vacuum-assisted container
grippers, air jets, a conveyor, a starwheel, a disk, an auger
device, and/or a Rivard shuttle, etc. That motion can be
intermittent and/or continuous. Container transport subsystem can
be powered non-electrically, such as magnetically and/or
fluidically (e.g., hydraulically and/or pneumatically), by for
example, one or more pneumatic slave cylinders that are each
coupled to a pneumatic master cylinder or actuator via one or more
lengths of pneumatic tubing. Any of the lengths of tubing can be
manually disassembleable without tools, sterilizable,
decontaminateable, and/or disposable.
[0078] In certain exemplary embodiments, a Rivard shuttle 2310
having a plurality of shuttle pins 2320 is implemented. At least a
portion of Rivard shuttle 2310 can be located in and/or immediately
adjacent critical zone 2200 and can move the vertical containers
from the outlet of container supply chute 2150 and advance them
through the series of processing stations. Rivard shuttle 2310 can
be powered non-electrically, such as hydraulically and/or
pneumatically, by for example, a pneumatic actuator 2390, which can
comprise a sterilizable pneumatic cylinder.
[0079] Rivard shuttle 2310 can provide an open architecture and/or
an absence of gears and/or hinges. In operation, Rivard shuttle
2310 can allow the containers to travel along a stationary rail
that can be perforated to facilitate laminar airflow and/or avoid
adding substantial impediments and/or turbulence to the airflow.
The containers can be advanced by a rod having notches on one side
for the container to seat into. Inserted perpendicularly into the
rod behind each notch can be a shuttle pin 2320 that can prod an
adjacent container along the rail when the rod is slid in a forward
direction. When the container has reached the next station, the rod
can rotate 90 degrees along its axis. When this occurs, the shuttle
pins are now pointed down (or upward if desired), thereby
disengaging from their adjacent containers, and the containers can
be bumped slightly away from the rod as the notches also rotate
down with the pins and the full surface of the rod now contacts the
container. The containers can seat into slight notches in a
guardrail at each station. While the container remains at a
particular station, the rod can slides in a reverse direction. The
rod can then rotate 90 degrees along its axis, which can return the
pins to the horizontal position. The rod is now prepared to move in
a forward direction again. When the rod moves in the forward
direction, the pins bump the containers out of the slight notches
at each station and prod the containers along to the next
station.
[0080] At least container entry position 2330, container fill
position 2340, and container first closure affixing position 2350
can be located in and/or adjacent critical zone 2200, the airflow
upstream of which can be substantially shielded from other
mechanical components of system 2000 and/or other systems. Exterior
shield 2420 and/or interior shield 2440 can be substantially solid,
clear, and/or formed of a material such as glass or plastic (e.g.
plexiglass, polycarbonate, etc.). Either of shields 2420, 2440 can
comprise appropriate ports for the entry into, and/or immediately
adjacent, critical zone 2200 of unfilled containers, filling needle
2460, closures, and/or the discharge from critical zone 2200 of
filled containers. Other ports may be provided for other purposes.
Either of shields 2420, 2440 can prevent contaminants from entering
the critical zone perpendicularly to the airflow.
[0081] Filling needle 2460 can be mounted directly on to a critical
zone shield 2420, 2440 and/or some other rigid surface. For
pharmaceutical purposes, filling needle 2460 can be constructed of
high-grade stainless steel, suitable for autoclaving. Filling
needle 2460 can be attached to shield 2420, 2440, etc. prior to
autoclaving to avoid handling after sterilization and the risk of
contamination. Filling needle 2460 can be disposable to avoid
cleaning issues. Filling needle can be coupled via one or more
lengths of tubing to a filling pump. Any of the lengths of tubing
can be disassembleable without tools, sterilizable, and/or
disposable. Filling can be automatically and/or intermittently
supplied through filling needle 2460 to the containers that pass a
filling station with which filling needle 2460 is associated.
[0082] System 2000 can comprise a first closure storage apparatus
2500, and potentially a second closure storage apparatus 2600, each
of which can hold and protect sterile closures. These closures may
be rubber stoppers, syringe plungers, screw caps, and/or over-caps,
etc. Thus, there can be multiple closure carousels when a closure
system contains more than one part, such as for example, a stopper
and over-cap. Because each closure storage apparatus can be
preloaded and covered prior to sterilization, the closures and/or
containers can be protected from handling and environmental
contaminates.
[0083] In certain exemplary embodiments, any closure storage
apparatus 2500, 2600 can be implemented as a carousel, hopper,
and/or vibrating bowl feeder, etc. An exemplary carousel can be
constructed using two pieces, a rack and a cover. The carousel can
hold between about 1 and about 1000 closures, including all values
and subranges therebetween. The closures can be pre-loaded onto the
carousel and the entire carousel covered prior to sterilization. If
constructed of appropriate materials, the carousel can be moist
heat sterilized to about 121 degrees C. Once sterilized, the
carousel can be place onto a closure carousel plate of system
2000.
[0084] A closure carousel can be milled from a solid cylinder of
aluminum, however, Teflon, welded 16-gage stainless steel sheet
(such as type 316L), or other materials of suitable strength and
rigidity may be substituted. The carousel can be ringed with
vertical slots that can hold closures. The base of the carousel can
be a solid disk except for one portal on the bottom that can allow
the closures to drop through. After a vertical row has emptied of
closures, the carousel can index to move a full vertical row of
closures over the open portal. The closures can promptly drop
through he portal and into a closure chute 2520, which can deliver
the closures to a closure provider/applier/inserter 2540, 2640.
[0085] In an exemplary embodiment, for a 20 mm diameter standard
rubber stopper, the outside carousel dimensions can be about 10
inch diameter.times.10 inches high. This carousel can have about 20
vertical slots, each holding 13 stoppers and thus holding a total
of about 260 stoppers. One additional, empty, and/or blank slot can
be included to enable the carousel to be transported without
stoppers dropping through the portal. Other sizes and modifications
are possible for the carousel, stoppers, syringe plungers, screw
caps, and/or over-caps.
[0086] Closure chute 2520 can orient and/or reorient (if necessary)
closures arriving from the closure storage apparatus 2500. Closure
chute 2520 can protect the closures from handling and contaminants.
Closure chute 2520 can be placed and/or attached onto frame 2800
prior to sterilization of frame 2800. Therefore, closure chute 2520
can be in place prior to the attachment of the closure storage
apparatus 2500. In certain exemplary embodiments, each closure
storage apparatus can have one or more closure chutes 2520
associated therewith. In certain exemplary embodiments, multiple
closure storage apparatus 2500, 2600 can share a single closure
chute 2520.
[0087] Closure chute 2520 can be shaped to accommodate each size of
closure used. Closure chute 2520 can be manufactured of solid or
welded stainless steel, such as type 316L, if the container chute
will be steam sterilized. Other materials of suitable strength and
rigidity may be substituted. These include Teflon and aluminum, for
example. Surfaces of closure chute 2520 can be smooth and slope
adjusted to assure that the closures are consistently presented to
the closure provider/applier/inserter 2540, 2640.
[0088] Each closure provider/applier/inserter 2540 can obtain
and/or lift a closure from its closure chute 2520, deposit the
closure on a container, partially insert the closure into the
container, fully insert the closure into the container, affix the
closure to the container, crimp the closure, etc. In certain
exemplary embodiments, a single device provides each desired
function, however, other embodiments may utilize a separate device
for certain functions. In the illustrated embodiment, a first
closure provider/applier/inserter 2540 affixes a first closure,
such as a stopper, to a container, and a second closure
provider/applier/inserter 2640, affixes a second closure, such as
an overcap, to the first closure.
[0089] Each closure provider/applier/inserter 2540, 2640 can
possess an absence of joints or other Class 100, 1000, and/or
10,000 particulate generators and/or contaminant generators in the
critical zone and/or the airflow upstream of the critical zone.
[0090] Each closure provider/applier/inserter 2540, 2640 can be
manufactured from stainless steel, such as type 316L stainless
steel, however, other suitable materials may be utilized. Each
closure provider/applier/inserter 2540, 2640 can be operated
non-electrically, such as via pneumatics, which can control the
specific movements of the closure provider/applier/inserter. In
certain exemplary embodiments, the closure
provider/applier/inserter can be hollow, with a hole located
underneath the tip, pointing down. A vacuum can be drawn through
the closure provider/applier/inserter that can lift the closure off
the closure chute. The closure provider/applier/inserter can be
pneumatically raised while remaining horizontal. When higher than
the level of the container, the closure provider/applier/inserter
can advance forward, through a port in interior shield 2440, until
the suspended closure is directly above the open container. The
closure provider/applier/inserter then can be lowered until it
affixes the closure upon the open container. The vacuum can be shut
off, and the closure inserter can be raised up, retracted, and then
lowered to grasp the next closure.
[0091] Upon exiting Rivard shuttle 2300, containers can enter a
container discharge chute 2700 that can accumulates containers
and/or deliver containers to a next processing station. Container
discharge chute 2700 can be pitched slightly down and away from the
exit of the Rivard Shuttle to allow for easier movement as the
containers crowd in. Container discharge chute 2700 can mount with
vertical pins on the bottom of container discharge chute 2700 that
can allow container discharge chute 2700 to be easily placed on
and/or removed from frame 2800.
[0092] FIG. 3 is a front view of an exemplary embodiment of a
system 3000, which can comprise a critical zone 3200, an operation
zone 3250, container transport subsystem 3300, and/or a frame 3800,
etc. An airflow 3900 can proceed relatively unimpeded by system
3000.
[0093] Container transport subsystem 3300 can transport containers
through a series of various processing stations, such as a
container entry position 3330, a container fill position 3340, a
container first closure affixing position 3350, a container dwell
position 3360, a container second closure affixing position 3370,
etc.
[0094] Container transport subsystem 3300 can comprise a Rivard
shuttle 3310 having a plurality of shuttle pins 3320. At least a
portion of Rivard shuttle 2310 can be located in and/or immediately
adjacent critical zone 3200. Rivard shuttle 2310 can be powered
non-electrically, such as hydraulically and/or pneumatically, by
for example, a pneumatic actuator 3390, which can comprise a
sterilizable pneumatic cylinder.
[0095] FIG. 4 is a block diagram of an exemplary embodiment of an
information device 4000, which can represent information device
1700 of FIG. 1. Information device 4000 can include well-known
components such as one or more communications interfaces 4100, one
or more processors 4200, one or more memories 4300 containing
instructions 4400, one or more input/output (I/O) devices 4500
coupled to one or more user interfaces 4600, etc.
[0096] As used herein, the term "information device" means any
device capable of processing information, such as any general
purpose and/or special purpose computer, such as a personal
computer, workstation, server, minicomputer, mainframe,
supercomputer, computer terminal, laptop, wearable computer, and/or
Personal Digital Assistant (PDA), mobile terminal, Bluetooth
device, communicator, "smart" phone (such as a Handspring Treo-like
device), messaging service (e.g., Blackberry) receiver, pager,
facsimile, cellular telephone, a traditional telephone, telephonic
device, programmable logic controller (PLC), a programmed
microprocessor or microcontroller and/or peripheral integrated
circuit elements, an ASIC or other integrated circuit, a hardware
electronic logic circuit such as a discrete element circuit, and/or
a programmable logic device such as a PLD, PLA, FPGA, or PAL, or
the like, etc. In general any device on which resides a finite
state machine capable of implementing at least a portion of a
method, structure, and/or or graphical user interface described
herein may be used as an information device.
[0097] As used herein, the term "communications interface" means
any device, system, or subsystem capable of coupling an information
device to a network and/or another information device. For example,
a communications interface can be a telephone, cellular phone,
cellular modem, telephone data modem, fax modem, wireless
transceiver, infrared transceiver, ethernet card, cable modem,
serial communications port, parallel communications port, PCMCIA
slot and/or card, digital subscriber line interface, bridge, hub,
router, or other similar device. Data and/or instructions
transferred via a communications interface can be in the form of
signals, which may be electronic, electromagnetic, optical, and/or
other signals capable of being received by a network interface.
Such signals can be provided to a network interface via a
communications path (i.e., channel), which can be implemented using
wire or cable, fiber optics, a phone line, a cellular phone link,
an RF link, an infrared link, and/or other communications
media.
[0098] As used herein, the term "processor" means a device for
processing machine-readable instruction. A processor can be a
central processing unit, a local processor, a remote processor,
parallel processors, and/or distributed processors, etc. The
processor can be a general-purpose microprocessor, such the Pentium
III series of microprocessors manufactured by the Intel Corporation
of Santa Clara, Calif. In another embodiment, the processor can be
an Application Specific Integrated Circuit (ASIC) or a Field
Programmable Gate Array (FPGA) that has been designed to implement
in its hardware and/or firmware at least a part of an embodiment
disclosed herein.
[0099] As used herein, a "memory device" means any hardware and/or
firmware element capable of storing data and/or instructions.
Memory devices can comprise non-volatile memory, volatile memory,
Random Access Memory, RAM, Read Only Memory, ROM, PROM, EPROM,
EEPROM, flash memory, magnetic media, a hard disk, a floppy disk, a
magnetic tape, an optical media, an optical disk, a compact disk, a
CD, a digital versatile disk, a DVD, and/or a raid array, etc. A
memory device can be removable, can include an interface (such as a
drive, controller, socket, driver software, etc.), and/or can
function as a computer-readable medium and/or as a machine-readable
medium.
[0100] As used herein, the term "firmware" means machine-readable
instructions that are stored in a read-only memory (ROM). ROM's can
comprise PROMs, EPROMs, and EEPROMs.
[0101] As used herein, the term "I/O device" means any device
capable of providing input to, and/or output from, an information
device. An I/O device can be any sensory-oriented input and/or
output device, such as an audio, visual, tactile (including
temperature, pressure, pain, texture, etc.), olfactory, and/or
taste-oriented device, including, for example, a monitor, display,
keyboard, keypad, touchpad, pointing device, microphone, speaker,
video camera, camera, scanner, and/or printer, potentially
including a port to which an I/O device can be attached or
connected.
[0102] As used herein, the term "user interface" means any device
for rendering information to a user and/or requesting information
from the user. A graphical user interface can include one or more
elements such as, for example, a window, title bar, panel, sheet,
tab, drawer, matrix, table, form, calendar, outline view, frame,
dialog box, static text, text box, list, pick list, pop-up list,
pull-down list, menu, tool bar, dock, check box, radio button,
hyperlink, browser, image, icon, button, control, dial, slider,
scroll bar, cursor, status bar, stepper, and/or progress indicator,
etc. An audio user interface can include a volume control, pitch
control, speed control, voice selector, voice recognition module,
speech controller, etc.
[0103] In certain exemplary embodiments, user interface 4600 of
information device 4000 can provide one or more elements for
programming, monitoring, alerting, adjusting, and/or logging any
activity of any component of any of systems 1000, 2000, and/or
3000, such as for example, the source of the airflow, the pump,
and/or the pneumatic cylinders (which can actuate the Rivard
shuttle, a carousel, and/or a closure inserter, etc.), etc. For
example, via user interface 4600 of information device 4000, the
step sequence can easily be set and/or manipulated to control the
timing of each step. If sensors are used, such as on the pneumatic
cylinders, information device 4000 can monitor each pneumatic
action and/or activate the pump at the appropriate time.
[0104] In certain exemplary embodiments, user interface 4600 can
provide a live operational status window of various operational
parameters; control of process instrumentation operation
on-the-fly; and/or control of multiple filling systems and/or
subsystems.
[0105] FIG. 5 is a flow chart of an exemplary embodiment of a
method 5000. At activity 5100, containers and/or closures can be
loaded and/or preloaded. The containers and/or closures can be
sterile. Activity 5200, a container can be shielded from
contaminants while outside and/or inside a critical zone. At
activity 5300, a container can be positioned at a desired station,
such as a station for purging, filling, closing, crimping, and/or
lyophilizing, etc. The station can be located in and/or immediately
adjacent a critical zone positioned in an airflow encountering no
Class 100, 1000, and/or 10,000 contaminant generators upstream from
the critical zone. At activity 5400, a filling can be introduced to
the container via a filling inlet (e.g., mouth, top, etc.) of the
container. At activity 5500, one or more closures can be affixed to
the container. Any one or group of activities 5100 through 5500 can
be repeated as desired. Any one or group of activities 5300 through
5500 can be performed in isolation from a human operator and/or
contaminants.
[0106] At activity 5600, the system can be manually disconnected,
such as from any pumping system and/or non-electrical power system
(e.g., pneumatic connections). At activity 5700, the system can be
manually loaded into a sterilization and/or decontamination device,
such as an autoclave. At activity 5800, the system can be
sterilized and/or decontaminated. At activity 5900, the system can
be manually connected, such as to a pumping system and/or
non-electrical power system, such that the system can be
operational again, and any one or group of activities 5100 through
5900 can be repeated as desired.
[0107] FIG. 6 is a top view of an exemplary embodiment of a
container positioning system 6000, which can comprise a Rivard
shuttle 6100 having a rod 6200, a stationary rail 6300, and/or a
guardrail 6400. Integrated into container positioning system 6000
and/or adjacent thereto can be a container entrance chute 6600
and/or a container exit chute 6700. Rod 6200 can comprise notches
6220 and/or shuttle pins 6240 that can engage with containers at
and/or between various processing stations. Stationary rail 6300
can define holes 6320 to allow the airflow to pass therethrough.
Guardrail 6400 can comprise notches 6420 that can engage with
containers at various processing stations.
[0108] FIG. 7 is a front view of an exemplary embodiment of a
Rivard shuttle 6100, such as that shown in FIG. 6. FIG. 8 is a top
view of an exemplary embodiment of a stationary rail 6300, which
can define holes 6320 to allow the airflow to pass therethrough.
FIG. 9 is a top view of an exemplary embodiment of a guardrail
6400, which can comprise notches 6420 that can engage with
containers at various processing stations. FIG. 10 is a top view of
an exemplary embodiment of a rod 6200, which can comprise notches
6220 and/or shuttle pins 6240 that can engage with containers at
and/or between various processing stations.
[0109] What follows is an exemplary operation sequence for certain
exemplary embodiments of an asceptic processing system ("machine")
described herein.
Set-Up:
[0110] Close the air system dump valve to supply air to a pneumatic
power system 1800. Supply air pressure can be about 80-100 PSI.
Regulated air pressure to the pneumatic power system 1800 can be
approximately 60-80 PSI.
[0111] Regulated air pressure to each pneumatically-driven
component of the machine can read approximately as follows: [0112]
ShuttleTravel--30 PSI [0113] Shuttle Pin Rotate--20 PSI [0114] Vial
Turntable--60 PSI [0115] Vial Turntable Cam--60 PSI [0116] Stopper
Pick-up Plate--40 PSI [0117] Stopper Pick-up Plate Cam--60 PSI
[0118] Stopper Insertion--40 PSI [0119] Stopper Arm Rotate--20 PSI
[0120] Stopper Pick-up Vacuum--60 PSI
[0121] With air pressure supplied to the machine, any of the
pneumatic cylinders may be cycled by pressing the manual over-ride
button on the pneumatic console for that cylinder.
[0122] Plug-in the machine to a 120V 60 Hz 20A power source.
[0123] Load the stopper bin with about 500 stoppers.
[0124] Load the vial turntable with one tray of vials, remove the
tray and place a second tray in the load position, and so on to
keep the turntable loaded with vials during operation.
Power On:
[0125] Twist to release the Power button. The button will
illuminate RED and electrical power will be supplied to the
machine.
[0126] Switch the power button on the laptop to the ON position and
its display will illuminate.
[0127] Open the air valve to supply air to the machine.
[0128] The pneumatic components of the machine will move to their
home positions.
Manual Single Step Mode:
[0129] With the machine stopped, press the Single Step button on
the laptop display. Starting with the first step in the sequence of
operation, the machine will proceed through one step of the
sequence at time each time the button is pressed. The pump fill
cycle will not be started during the Single Step Mode.
Cycle Pump:
[0130] With the machine stopped, press the Cycle Pump button to
start the pump fill cycle. Note: a vial must be in position for the
pump to cycle. Only the pump will operate and when the cycle is
complete, the machine will wait for the next command from the
operator.
Single Cycle Mode:
[0131] With the machine stopped, press the Single Cycle button on
the laptop display. Press YES or NO to confirm whether or not the
pump fill cycle is to be started as the machine runs. Starting with
the first step in the sequence of operation, the machine will
proceed through one complete cycle and then stop. One complete
cycle will be made each time the Single Cycle button is
pressed.
Automatic Run Mode:
[0132] With the machine stopped, press the Run button. Press the
YES or No to confirm whether or not the pump fill cycle is to be
started as the machine runs. The machine will begin normal
operation and will continue until stopped by the operator, stopped
by a shortage of vials or stoppers, or stopped by a condition which
has prevented a sensor from supplying an expected input when needed
in the sequence (see diagnostics).
Normal Sequence of Operation:
[0133] At power-up all cylinders will move to the home position, as
follows: TABLE-US-00002 Pneumatic Cylinder Position Sensor Input On
Shuttle Pin Rotate Extended On Shuffle Travel Retracted On Vial
Turntable Retracted On Vial Turntable Cam Retracted On Stopper
Pick-up Plate Retracted On Stopper Pick-up Plate Cam Refracted On
Stopper Insertion Refracted On Stopper Rotate Extended On Stopper
Pick-up Vacuum Off N/A
[0134] Input sensors will indicate key machine conditions, as
follows: TABLE-US-00003 Vial Present Off Stopper Present Off
Stopper Queue Off
[0135] When the Run Mode is selected, the following events occur
automatically (these events may be selected one at a time by using
the Single Step Mode):
[0136] The vial turntable cam cylinder will extend to set the cam
against the turntable drive plate. The vial turntable cylinder will
extend causing the turntable to rotate. When the turntable cylinder
has reached the end of its stroke, the cam cylinder will retract
and then the turntable cylinder will retract. These events will
continue repeatedly while the machine is in run mode to bring vials
to the queue position of the shuttle. (Note: the vial turntable
cylinder typically should finish retracting and start extending
prior to the shuttle travel cylinder extending. This will keep
pressure against the next vial to be picked-up by the shuttle at
the time of pick-up.)
[0137] The stopper pick-up plate cam cylinder will extend to set
the cam against the stopper pick-up drive plate. The stopper
pick-up plate cylinder will extend to rotate causing stoppers to be
picked-up and allowing stoppers to fill the dispensing chute. When
the pick-up plate cylinder has reached the end of its stroke, the
cam cylinder will retract and then the pick-up plate cylinder will
retract. When the dispensing chute is filled with enough stoppers,
the Stopper Queue Input sensor will illuminate On causing the
stopper pick-up plate to stop rotation at the end of its cycle.
When this sensor no longer detects the presence of stoppers in the
dispensing chute, rotation of the stopper pick-up plate will resume
immediately.
[0138] When stoppers reach the bottom of the stopper dispensing
chute, the stopper present input sensor will illuminate On
indicating that a stopper is present and the stopper components of
the machine are ready for a vial.
[0139] With the stopper present sensor on, the shuttle pin rotate
cylinder retracts causing the pins on the shuttle rod to rotate to
the up (push) position.
[0140] The shuttle travel cylinder extends causing the shuttle to
index a vial from the queue position to the fill position.
[0141] The shuttle pin rotate cylinder extends causing the shuttle
pins to rotate to the down position. This positions the vial in its
nest for filling or for stopper insertion, and allows the shuttle
travel rod to return to the home position to pick-up the next
vial.
[0142] The vial present input sensor illuminates when a vial is
present, causing an output to the pump to begin the pre-programmed
pump fill cycle. (If no vial is present, there is no input and the
pump is not started. The vial present input sensor looks for a vial
on the next index of the shuttle. If no vial was filled, then no
attempt will be made to insert a stopper on the next index of the
shuttle. If no vial is present on the third index of the shuttle,
the run cycle will stop and an alarm will appear on the laptop
display.)
[0143] The shuttle travel cylinder retracts returning the shuttle
to pick-up the next vial. (Note: with the pins in the down
position, the shuttle can return to the home position while the
pump cycle is in progress.)
[0144] When the pump fill cycle has finished, the shuttle pin
rotate cylinder retracts causing the pins to rotate to the up
position; and the shuttle travel cylinder extends to move an empty
vial from the queue position to the fill position and to move a
filled vial from the fill position to the stopper position.
[0145] If a vial is present the pump fill cycle is started.
[0146] If a vial was filled on the previous cycle, a stopper is
placed on the filled vial as follows (these actions are taking
place while the vial is being filled so that the stopper is waiting
over-top of the filled vial as it moves into the stopper position
on the shuttle).
[0147] The stopper insert cylinder extends to pickup a stopper.
[0148] Vacuum is turned On
[0149] The stopper insert cylinder retracts.
[0150] The stopper rotate cylinder extends to position the stopper
insert arm over the filled vial.
[0151] The stopper insert cylinder extends to press the stopper
onto the filled vial.
[0152] Vacuum is turned Off.
[0153] The stopper insert cylinder retracts.
[0154] The stopper rotate cylinder retracts and is ready to pick-up
the next stopper.
[0155] When the pump fill cycle is finished the shuttle indexes to
move another vial from the queue position to the fill position, to
move a filled vial from the fill position to the stopper position,
and to move a stoppered vial from the stopper position toward the
shuttle discharge position where the vial moves from the shuttle
into a collection tray.
[0156] A total count is maintained of vials filled during the
run.
[0157] A cycle count of filled vials is made to determine when the
number of vials needed to complete a tray has been filled. When
this number of vials has been filled and has been indexed to the
discharge position, the machine will stop until the operator
replaces the tray and presses the Batch Complete button and then
the Automatic button to resume processing. Note: the machine will
pause prior to the fill cycle of the next vial so a filled vial
does not wait exposed to air while the tray is being changed. At
the end of a run, vials remaining in the shuttle can be lifted out
or cleared by running the Single Step Mode.
Shut-Down:
[0158] Press the POWER button to turn the system off. This button
kills all electrical power to the machine.
[0159] Still other embodiments will become readily apparent to
those skilled in this art from reading the above-recited detailed
description and drawings of certain exemplary embodiments. It
should be understood that numerous variations, modifications, and
additional embodiments are possible, and accordingly, all such
variations, modifications, and embodiments are to be regarded as
being within the spirit and scope of the appended claims. For
example, regardless of the content of any portion (e.g., title,
field, background, summary, abstract, drawing figure, etc.) of this
application, unless clearly specified to the contrary, there is no
requirement for the inclusion in any claim of the application of
any particular described or illustrated activity or element, any
particular sequence of such activities, or any particular
interrelationship of such elements. Moreover, any activity can be
repeated, any activity can be performed by multiple entities,
and/or any element can be duplicated. Further, any activity or
element can be excluded, the sequence of activities can vary,
and/or the interrelationship of elements can vary. Accordingly, the
descriptions and drawings are to be regarded as illustrative in
nature, and not as restrictive. Moreover, when any number or range
is described herein, unless clearly stated otherwise, that number
or range is approximate. When any range is described herein, unless
clearly stated otherwise, that range includes all values therein
and all subranges therein. Any information in any material (e.g., a
United States patent, United States patent application, book,
article, etc.) that has been incorporated by reference herein, is
only incorporated by reference to the extent that no conflict
exists between such information and the other statements and
drawings set forth herein. In the event of such conflict, including
a conflict that would render a claim invalid, then any such
conflicting information in such incorporated by reference material
is specifically not incorporated by reference herein.
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