Note: Descriptions are shown in the official language in which they were submitted.
CA 02785991 2016-02-23
DEVICE AND METHOD FOR AUTOMATICALLY OPENING AND CLOSING A
MATERIAL CONTAINER DURING A LYOPHILIZATION PROCESS
FIELD OF THE DISCLOSURE
[0002] The present disclosure is generally directed to devices, systems, and
methods for
lyophilizing materials and, more particularly, to devices, systems, and
methods for
automatically aseptically sealing materials before and after a lyophilization
process, while
automatically unsealing for a lyophilization step.
BACKGROUND
[0003] Lyophilization, which can also be referred to as freeze-drying, is a
dehydration
process typically used to preserve a perishable material or make the material
more
convenient for transport. Lyophilization works by freezing the material and
then reducing
the surrounding pressure and adding sufficient heat to allow the frozen water
in the
material to sublimate, i.e., transition, directly from a solid to a gas. The
gas is then
removed from the material to complete the dehydration.
[0004] Conventional lyophilization processes are carried out with freeze-
drying machines
located within laboratories or production facilities, for example, and which
define internal
chambers for containing the material to be lyophilized. The material to be
lyophilized will
often be formulated within production facilities and then introduced into the
lyophilization chamber in open vessels such as vials, bottles, or other
containers. As such,
the gas can easily exhaust from the open vessels during the lyophilization
process.
[0005] In the pharmaceutical industry materials that are lyophilized, however,
require
more careful handling to prevent contamination. For example, the
pharmaceuticals should
be contained in sterile environment while being transported through the
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laboratories or production facilities before and after lyopholization. The
containers in
which the substance which is to be lyophilized is contained may form a part of
a sterile
barrier between the substance and the environment, but such containers must be
open to
enable the gas to exhaust therefrom during lyophilization.
100061 For medical containers such a vials, the containment in the sterile
environment
is maintained using different techniques. For example, prior to going into the
lyophilization chamber the vials are filled in a fill room which maintains a
sterile
environment. Stoppers are then partially inserted into the opening or mouth of
the vial.
The stoppers are constructed in such a manner that even though the stoppers
are partially
inserted, a passageway for gas to flow into and out of the interior of the
vial is
maintained. The vials are then moved into the lyophilization chamber. The
lyophilization process is then conducted. Prior to exit from the
lyophilization chamber
the shelf on which the vials sit moves upward toward the lower planar surface
of the
immediately adjacent overhead shelf, with that surface contacting and pushing
the
stoppers further into the mouth of the vial to fully seal the interior of the
vial from the
environment. The vials may then be removed from the lyophilization chamber
into a
non-sterile environment.
100071 For other containers such as syringes, or flexible containers or bags,
such a
process of partially inserting stoppers into the mouth and then fully sealing
the containers
prior to exit from the lyophilization chamber is not practical. Syringes
utilize pistons that
generally require a configuration which does not lend itself to partial
insertion while still
maintaining a gas flow passageway. Flexible containers may not have the
rigidity to
withstand the force necessary to fully insert a stopper without buckling.
100081 Therefore, to maintain sterility these containers must be maintained in
a sterile
environment upon exit from the lyophilization chamber, until such containers
reach a
sterile environment for further sealing. Providing such a sterile environment
immediately
adjacent the lyophilization chamber greatly increases the expense and
complexity of such
production facilities.
[0009] Therefore, there is a need for a device and process which allows for
the interior
of a container to be open during the lyophilization cycle but maintains the
open containers
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in a sterile environment after such cycle such that they may be transported to
a sterile
environment remote from the lyophilization chamber while still maintaining the
sterility
of the interior of the containers.
[0009a] Accordingly, in one aspect of the present invention there is
provided a
device for storing a material to be lyophilized, the device comprising:
a support panel;
a sidewall attached to and extending from the support panel, the sidewall and
the
support panel defining a storage space for accommodating a material;
an opening defined by a rim of the sidewall that is spaced away from the
support
panel;
a cover removably disposed adjacent to the rim of the sidewall for closing the
opening;
at least one biasing member coupled to the cover, and biasing the cover into
the
closed position;
at least one lifter device disposed between the support panel and the cover
and
comprising a reservoir and at least one movable wall, the reservoir defining a
sealed
cavity containing a fluid, the at least one movable wall in operable
communication with
the fluid in the sealed cavity and operatively engaging the cover to displace
the cover
away from the rim when the at least one lifter device is subject to an ambient
pressure
that is less than the pressure of the fluid in the sealed cavity; and
wherein the at least one lifter device includes a gasket disposed between the
cover
and the rim of the sidewall adjacent to the opening for sealing at least a
perimeter portion
of the opening when the cover is in the closed position.
[0009b] According to another aspect of the present invention there is
provided a
method of facilitating the lyophilization of a material, the method
comprising:
loading the material into a material container having a rim and a removable
cover
disposed adjacent to the rim, the material container defining storage space
and at least one
lifter device being disposed within the storage space;
loading the material container into a lyophilization chamber of a freeze
drying
machine while the removable cover is in a closed position engaging the rim;
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lyophilizing the material;
operatively engaging the cover with the at least one lifting device and
automatically lifting the cover into an opened position spaced from the rim of
the
container by reducing the ambient pressure in the lyophilization chamber while
lyophilizing the material to allow at least one component of the material to
exhaust from
the container, wherein automatically lifting the cover into an opened position
comprises
generating a lifting force with a movable wall of the at least one lifter
device by
expanding a fluid within a sealed cavity defined by the at least one lifter
device; and
automatically returning the cover to the closed position engaging the rim of
the
container after lyophilizing the material by raising the ambient pressure in
the
lyophilization chamber, wherein automatically returning the cover to the
closed position
comprises increasing the ambient pressure in the lyophilization chamber such
that, while
the cover is still in the open position, the ambient pressure within the
storage space also
increases and the fluid within the sealed cavity defined by the at least one
lifter device
compresses and draws the movable wall back to return the cover to the closed
position.
SUMMARY
[0010] One aspect of the present disclosure provides a device for storing a
material to
be lyophilized. The device generally includes a support panel, a sidewall, an
opening, a
cover, and at least one lifter device. The sidewall extends transverse to the
support panel.
The sidewall and the support panel define a storage space for accommodating a
material.
The opening is defined by a rim of the sidewall that is spaced away from the
support
panel. The cover is removably disposed adjacent to the rim of the sidewall for
closing the
opening. The at least one lifter device is disposed between the support panel
and the
cover and includes a reservoir and at least one movable wall. The reservoir
defines a
sealed cavity containing a fluid. The at least one movable wall is in operable
communication with the fluid in the sealed cavity and operatively engaging the
cover to
displace the cover away from the rim when the at least one lifter device is
subject to an
ambient pressure that is less than the pressure of the fluid in the sealed
cavity.
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[00111 The at least one lifter device can optionally include a cylinder and a
sealing
piston slidably disposed relative to the cylinder. The cylinder defines the
reservoir and
the cavity, and the piston defines the movable wall.
[0012] The lifter device can include a syringe such that the cylinder
comprises a
syringe tube and the piston comprises a syringe plunger.
[0013] The at least one lifter device can include a bellows defining the
sealed cavity.
[0014] The device can further include a gasket disposed between the cover and
the rim
of the sidewall adjacent to the opening for sealing the opening when the cover
is the
closed position.
[0015] The gasket can be attached to and extend around a perimeter portion of
the
cover.
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[0016] The gasket can define the at least one lifter device and include a
tubular gasket
defining the sealed cavity and a resilient sidewall portion defining the at
least one
movable wall.
[0017] The sidewall can include four sidewall panels arranged such that the
sidewall
has a generally square or rectangular cross-section.
[0018] The at least one lifter device can include four lifter devices, each
lifter device
being disposed within a corner defined by an adjacent pair of the sidewall
panels.
[0019] The device can further include at least one member coupled to the cover
and
biasing the cover into the closed position.
[0020] The at least one biasing member can include four springs, each spring
having a
first end coupled to the cover and a second end coupled to the sidewall or the
support
panel for biasing the cover into the closed position.
[0021] The at least one biasing member can include at least one of a
compression
spring, an elastic cord, and a rubber band.
[0022] Another aspect of the present disclosure includes a system for
lyophilizing
material. The system generally includes a freeze drying machine defining a
chamber, and
a device of any of the foregoing aspects, wherein the device is adapted to be
disposed in
the chamber.
100231 Another aspect of the present disclosure includes a method of
facilitating the
lyophilization of a material. The method includes loading the material into a
material
container having a rim and a removable cover disposed adjacent to the rim. The
method
further includes loading the material container into a lyophilization chamber
of a freeze
drying machine while the removable cover is in a closed position engaging the
rim. The
method further includes lyophilizing the material and automatically lifting
the cover into
an opened position spaced from the rim of the container by reducing the
ambient pressure
in the lyophilization chamber while lyophilizing the material to allow at
least one
component of the material to exhaust from the container. The method further
includes
automatically returning the cover to the closed position engaging the rim of
the container
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after lyophilizing the material by raising the ambient pressure in the
lyophilization
chamber.
[0024] Automatically lifting the cover into an opened position can optionally
include
generating a lifting force with a movable wall of at least one lifter device
that is disposed
adjacent to the cover by expanding a fluid within a sealed cavity of the at
least one lifter
device.
[0025] Generating a lifting force with a movable wall can include generating a
lifting
force with a sealing piston that is at least partly slidably disposed within a
cylinder by
expanding a fluid within a sealed cavity of the cylinder.
[0026] Generating a lifting force with a movable wall can include generating a
lifting
force with a cover that is operably connected to a bellow by expanding a fluid
within a
sealed cavity of the bellows.
[0027] Generating a lifting force with a movable wall can include generating a
lifting
force with a resilient sidewall portion of a tubular gasket by expanding a
fluid within a
sealed cavity of the tubular gasket.
[0028] The method can further include urging the cover into the closed
position with a
closing force that is smaller than the lifting force.
[0029] Urging the cover into the closed position can include urging the cover
into the
closed position with at least one biasing member coupled to the cover and the
container.
[0030] Urging the cover into the closed position can include establishing a
pressure in
the lyophilization chamber that is at least equal to the pressure of the fluid
in the sealed
cavity of the lifter device.
[0031] Urging the cover into the closed position can include establishing a
pressure in
the lyophilization chamber that is greater than the pressure of the fluid in
the sealed cavity
of the lifter device.
[0032] The method can further include restoring the pressure in the
lyophilization
chamber after lyophilizing the material such that the closing force overcomes
the lifting
force and urges the cover into the closed position.
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BRIEF DESCRIPTION OF THE DRAWINGS
[0033] Fig. 1 is a perspective view of a system for lyophilizing material
constructed in
accordance with the principles of the present disclosure and including a
freeze-dryer and
a lyophilization chamber accommodating a container adapted to contain the
material to be
lyophilized;
[0034] Fig. 2 is a cross-sectional view of the container of Fig. 1 constructed
in
accordance with the principles of the present disclosure and including a
plurality of lifter
devices occupying a first position such that a cover of the container is in a
closed
position;
100351 Fig. 3 is a top view of the container of Figs. 1 and 2 with its cover
lifted;
[0036] Fig. 4 is a cross-sectional view of the container of Figs. 1-3
including the
plurality of lifter devices occupying a second position such that the cover of
the container
is in an opened position;
[0037] Fig. 5 is a detail view of an alternative embodiment of the lifter
devices of the
container of Figs. 2 -4;
[0038] Fig. 6 is a cross-sectional side view of an alternative embodiment of a
container
constructed in accordance with the principles of the present disclosure
including a lifter
device occupying a first position such that the cover of the container is in a
closed
position;
[0039] Fig. 7 is a cross-sectional view of the container of Fig. 6 including
the lifter
device occupying a second position such that the cover of the container is in
an opened
position;
[0040] Fig. 8 is a side view of the container of Fig. 7 taken from the
perspective of line
VIII-VIII of Fig. 7;
[0041] Fig. 9 is a cross-sectional side view of another alternative embodiment
of a
container constructed in accordance with the principles of the present
disclosure,
including a plurality of lifter devices occupying a first position such that a
cover of the
container is in a closed position; and
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100421 Fig. 10 is a cross-sectional side view of a container constructed in
accordance
with the principles of the present disclosure and including a filter attached
to the cover for
enabling the flow of fluid out of the container during lyophilization.
DETAILED DESCRIPTION
100431 Fig. 1 depicts a system 1 for lyophilizing material and including a
freeze-drying
machine 10 accommodating a container 100, which is adapted to contain the
material to
be lyophilized. The freeze-dryer 10 defines a lyophilization chamber 12 that
is
selectively openable/closeable with a door 14, for example in a conventional
manner.
The container 100 is disposed within the lyophilization chamber 12 such that
any material
carried within the container 100 can be lyophilized after the door 14 is
closed and the
freeze-drying machine 10 is activated. To lyophilize the material in the
container 100,
the freeze-drying machine 10 reduces the temperature within the lyophilization
chamber
12 to a temperature in the range of approximately negative fifty degrees
Celsius (-50 C)
to approximately negative eighty degrees Celsius (-80 C), for example. Then,
the
ambient pressure of the lyophilization chamber 12 is reduced with a vacuum
pump 16, for
example, to a pressure that is substantially less than atmospheric pressure,
such as a
pressure in the range of approximately 1.33 Pa (0.01 Ton-) to approximately
133 Pa (1
Torr). With the ambient pressure reduced, a sufficient amount of heat is added
to the
lyophilization chamber 12 to sublimate the frozen water in the material from a
solid to a
gas. The gas can be removed from the material and collected on a condenser
plate, for
example, such that the material remains "freeze-dried." The pressure within
the
lyophilization chamber 12 can then be increased or returned to the ambient
pressure that
is outside of the lyophilization chamber 12, and the dried material can be
removed from
the freeze-drying machine 10.
100441 Referring now to Figs. 2-4, one embodiment of the container 100
depicted in
Fig. 1 will be described. The container 100 is generally arranged and
configured to
provide a sealed environment for transporting material to be lyophilized, or
material that
has already been lyophilized. Such materials can include pharmaceuticals or
bio-
materials, for example. The present disclosure is not limited to being used
with such
materials, however, and can be used to lyophilize generally any desired
material.
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100451 The container 100 generally includes a tub 102, a cover 104, a gasket
106, first
through eighth biasing members such as springs 108a-108h (see Figs. 1 and 2),
and first
through fourth lifter devices 110a-110d (see Figs. 2 and 3). Only the fifth
and seventh
biasing members 108e, 108g are illustrated in Fig. 2 for the sake of clarity.
Moreover, as
illustrated, the present embodiment of the container 100 includes a storage
space 130 that
is adapted to contain a plurality of vessels 112 of material 114. The vessels
112 are each
depicted as including a syringe tube suspended from a support plate 101, for
example, but
other embodiments can include generally any type of container for holding the
material
114. For example, the vessels 112 can include vials, beakers, cups, bowls,
trays or any
plurality of material handling devices whether suspended from a support plate
or
otherwise supported within the storage space 130. Moreover, in some
embodiments, the
container 100 does not necessarily have to be adapted to accommodate a
plurality of
vessels 112, but rather, can contain a single vessel 112 containing material
114. The
single vessel 112 can include a pan, a bowl, a beaker, a tray, or generally
any other
material handling device. In still further embodiments, the tub 102 of the
container 100
itself can directly contain the material 114, thereby eliminating the need for
any
intervening vessel 112.
100461 The tub 102 includes a support panel 116 and a sidewall 118 extending
upward
from around the periphery and the support panel 116. The tub 102 of the
present
embodiment is generally box-shaped with a rectangular or square horizontal
cross-
section, and therefore, the sidewall 118 includes first through fourth
sidewall panels 120a-
120d. As depicted in Fig. 2, each sidewall panel 120a-120d includes a stepped
outer
profile constructed by a lower sidewall portion 122 and an upper sidewall
portion 124.
The upper sidewall portion 124 includes an upper horizontal surface 126 that
defines a
rim 128 of the sidewall 118. The rim 128 defines an opening 132 of the tub
102, which is
in communication with the storage space 130 containing the vessels 112. The
lower
sidewall portion 122 includes a lip 103 extending into the storage space 130
and
supporting the support plate 101 suspending the vessels 112.
[0047] The cover 104 is a generally flat structure shaped to at least
correspond with the
cross-sectional shape of the tub 102. More specifically, the cover 104 is
shaped to at least
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correspond to the shape of the rim 128 of the tub 102 such that the cover 104
can close
the tub 102 and seal the storage space 130 against contamination. In the
present
embodiment, this seal is facilitated by the gasket 106, which is attached to
the outer
periphery of the cover 104 and adapted to sealingly engage the rim 128 of the
tub 102. In
other embodiments, the optional gasket 106 can be attached to the rim 128 and
adapted to
sealingly engage the outer periphery of the cover 104. The gasket 106 can be
constructed
of generally any type of material capable of creating a fluid and/or air tight
seal between
the cover 104 and the rim 128 such as an elastomer, a rubber, a cork, or
generally any
other material. While the gasket 106 is depicted as having a generally square
cross-
section, gaskets with other cross-sectional shapes are intended to be within
the scope of
the present disclosure. That is, the gasket 106 can have a rectangular cross-
section, a
circular cross-section, or generally any other foreseeable shape cross-
section.
100481 The first through eighth biasing members 108a-108h are spaced about the
outer
periphery of the tub 102 for urging the cover 104 into the closed position
depicted in Fig.
2 and maintaining the closed position. Each of the biasing members 108a-108h
can
include a coil spring, a rubber or other elastic element (e.g., a rubber band,
an elastic
cord), or generally any other type of element capable of serving the intended
purpose.
100491 As shown in Fig. 2, each of the first through eighth biasing members
108a-108h
includes a first end 134 connected to the cover 104 and a second end 136
connected to the
tub 102. More specifically, the first end 134 of each member 108a-108h
includes a first
hook 138 extending around a first pin 140 extending from the cover 104. The
second end
136 of each member 108a-108h includes a second hook 142 extending around a
second
pin 144 extending from the sidewall 118 of the tub 102. Accordingly, it should
be
appreciated that the cover 104 includes eight first pins 140, and the tub 102
includes eight
second pins 144.
100501 While the present embodiment includes the second ends 136 of the
members
108a-108h connected to the sidewall 118 of the tub 102 and, more particularly,
the upper
portions 124 of the sidewall panels 120a-120d, in alternative embodiments, the
second
ends 136 of the members 108a-108h can be connected to the support panel 116 or
any
other portion of the tub 102, for example. Moreover, while the members 108a-
108h are
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connected to the tub 102 and cover 104 with hooks 138, 142 and pins 140, 144,
any
means for making such a connection is intended to be within the scope of the
present
disclosure. In an alternative embodiment, the cover can be hinged to the tub
102, and
preferably employ fewer biasing members and lifter devices.
[0051] The first through fourth lifter devices 110a-110d of the present
embodiment are
positioned within corners of the storage space 130 of the tub 102 and
supported on the
support panel 116. As depicted in Fig. 2, each lifter device 110a-110d of the
present
embodiment includes a cylinder 146 and a piston 148 at least partly slidably
disposed in
the cylinder 146. The cylinder 146 includes a reservoir 150 defining a cavity
152
containing a fluid at a pressure that is equivalent to atmospheric pressure of
approximately 101 kPa (760 Torr). The fluid in the cavity 152 can include a
gas such as
air, for example, a liquid, or some combination of liquid and gas. The piston
148 includes
an elongated member slidably disposed within the cylinder 146 and carrying a
seal 154
sealingly engaging the inside wall of the cylinder 146, thereby defining the
cavity 152 as
a sealed cavity. Each piston 148 further defines a movable wall 156 on an end
thereof,
opposite the cylinder 146.
[0052] With the container 100 configured as described, the lifter devices 110
are
capable of automatically moving from a first position (Fig. 2) to a second
position (Fig. 4)
to move the cover 104 from a closed state engaging the rim 128 (Fig. 2) to an
open state
spaced from the rim 128 (Fig. 4) while the material 114 disposed within the
vessels 112
undergoes a lyophilization process.
[0053] For example, as discussed above, any lyophilization process conducted
by the
freeze-drying machine 10 depicted in Fig. 1, for example, includes reducing
the pressure
within the lyophilization chamber 12 to a pressure substantially less than
atmospheric
pressure, therefore, substantially less than the pressure in the sealed
cavities 152 of the
cylinders 146 of the lifter devices 110. In some embodiments, the pressure
within the
lyophilization chamber 12 can be reduced to a pressure in the range of
approximately
1.33 Pa (0.01 Torr) to approximately 133 Pa (1 Ton) by activating the vacuum
pump 16.
Other ranges between atmospheric pressure and absolute vacuum are intended to
be
within the scope of the present disclosure.
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[0054] In the present embodiment of the container 100 described with reference
to
Figs. 2-4, the foregoing reduction in pressure within the lyophilization
chamber 12 is also
communicated to the storage space 130 of the container 100. In some
embodiments, the
reduction in pressure in the lyophilization chamber 12 can be communicated to
the
storage space 130 of the container 100 via a one-way check valve 158 disposed
within a
through-bore 160 in the upper portion 124 of the fourth sidewall panel 120d of
the
sidewall 118. The check valve 158 is configured to enable the flow of fluid
out of the
storage space 130 of the container 100, but prevent fluid from flowing into
the storage
space 130. A filter 159 may also be included with the check valve to prevent
the passage
of any microbes through the check valve, should a leakage occur. The filter
159
preferably has a 20 micron pore size. The filter 159 may also be used without
a check
valve. As such, contaminants cannot penetrate the tub 102 when the cover 104
is in the
closed position and it is being transported through a laboratory or production
facility, for
example. While the embodiment depicted in Figs. 2-4 includes the through-bore
160, the
optional filter 159, and the optional check valve 158 disposed within the
upper portion
124 of the fourth sidewall panel 120d of the sidewall 118 of the container
100, alternative
embodiments can be arranged differently. For example, Fig. 10 depicts an
alternative
embodiment of the container 100 wherein the cover 104 includes the through-
bore 160
and a filter 1159. The embodiment of Fig. 10 could also optionally include a
check-
valve, for example, one implemented in a manner similar to check-valve 158
described
above. While Figs. 2-4 disclose the through-bore 160 disposed in the sidewall
118 of the
container 100 at location adjacent to the cover 104, and Fig. 10 discloses the
through-bore
160 in the cover 104 itself, the through-bore 160 does not necessarily have to
be
positioned near or in the cover 104. For example, the through-bore 160, as
well as the
optional filter 159, 1159, can be located in generally any wall of the
container 100 that
communicates with the storage space 130.
[00551 As the pressure within the storage space 130 is reduced below
atmospheric
pressure, which is also the pressure in the sealed cavities 152 of the
cylinders 146 of the
lifter devices 110, the fluid (e.g., a gas) in each of the sealed cavities 152
automatically
expands and moves the corresponding piston 148 partly out of the cylinder 146
from the
first position (Fig. 2) to the second position (Fig. 4). While the pistons 148
move from
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the first position to the second position, the movable walls 156 engage the
cover 104, as
shown, to move the cover 104 from the closed position (Fig. 2) to the opened
position
(Fig. 4). When the cover 104 is in the opened position, the storage space 130
of the tub
102 is in open communication with the ambient atmosphere of the lyophilization
chamber
12. Accordingly, as the frozen water within the material 114 in the vessels
112
sublimates to a gas during lyophilization, the gas is free to exhaust from the
vessels 12
and the storage space 130, as illustrated in Fig. 4.
[0056] After a suitable lyophilization cycle, which can be chosen by a person
of
ordinary skill in the art, the freeze-drying machine 10 then raises the
ambient pressure
within the lyophilization chamber 12. In some embodiments, the pressure in the
lyophilization chamber 12 can be raised by deactivating the vacuum pump 16 and
opening a vent, for example, to allow the pressure to stabilize relative to
the pressure
outside the freeze-drying machine 10. In some embodiments, the pressure in the
lyophilization chamber 12 is raised to be substantially equal to atmospheric
pressure, i.e.,
101 kPa. As the ambient pressure within the lyophilization chamber 12
increases, the
ambient pressure within the storage space 130 of the tub 102 increases because
the cover
104 is in the opened position and the fluid within the sealed cavities 152 of
the cylinders
146 of the lifter devices 110 compresses and draws the pistons 148 back toward
the first
position (Fig. 2). As the pistons 146 return to the first position, the
biasing members
108a-108g automatically urge the cover 104 back to the closed position (Fig.
2). With the
cover 104 in the closed position, the gasket 106 provides a fluid tight seal
against the rim
128 of the tub 102 and prevents communication between the storage space 130
and the
surrounding environment. The container 100 can then be safely removed from the
lyophilization chamber 12 and transported about the laboratory or production
facility
without concern for contaminating the lyophilized material 114.
[0057] While the lifter devices 110 of the container 100 disclosed in Figs. 2-
4 include
simple cylinders 146 and pistons 148, alternative embodiments of the lifter
devices 110
can be constructed differently. For example, Fig. 5 depicts an alternative
lifter device 210
that could be used in a manner generally identical to that described above
with respect to
the lifter devices 110 depicted in Figs. 2-4.
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[0058] The lifter device 210 depicted in Fig. 5 generally includes a
conventional
syringe 260 including a syringe tube 262 and a plunger 264 partly slidably
disposed
within the syringe tube 262. The syringe tube 262 includes a reservoir 250
defining a
cavity 252 containing a fluid, for example, at a pressure that is equivalent
to atmospheric
pressure (101 kPa). The plunger 264 includes an elongated member slidably
disposed
within the syringe tube 262 and having a sealing disk 254, a stem 256, and a
movable
wall 258. The sealing disk 254 engages the inside wall of the syringe tube 262
to provide
a fluid tight seal, thereby defining the cavity 252 as a sealed cavity.
[0059] In some alternative embodiments, the lifter device 210 of Fig. 5 can
further
include a bellows 268, which is shown with dashed lines in Fig. 5, disposed
within the
cavity 252 of the syringe tube 262. The bellows 268 can include a sack formed
in an
accordion-like configuration and containing the fluid, for example, that
defines the sealed
cavity 252 of the lifter device 210. As such, the bellows 268 is expandable
and
contractable in response to changes in the ambient pressure for moving the
plunger 264 in
and out of the syringe tube 262 for moving the cover 104 between the opened
and closed
positions. Therefore, when the bellows 268 is included within the lifter
device 210, the
sealing disk 254 does not need to provide a fluid-tight seal against the
syringe tube 262.
[0060] As shown, the
lifter device 210 of Fig. 5 can be supported on the support panel
116 of the tub 102 depicted in Fig. 2, for example. Moreover, the movable wall
258 of
the plunger 264 can be disposed in engagement with the cover 104 for moving
the cover
104 from the closed position to the opened position in a manner identical to
that described
above. In alternative embodiments, the syringe 260 of Fig. 5 can be suspended
from the
support plate 101 depicted in Fig. 2 in a manner identical to the vessels 112
of Fig. 2.
[0061] While the lifter devices 110, 210 have thus far been described as being
disposed
within the storage space 130 of the tube 102 of the container 100, in
alternative
embodiments, these lifter devices 110, 210 could be reduced in size, for
example, and
disposed between the rim 128 of the tub 102 and the cover 104 at a location
adjacent to
the gasket 106 depicted in Fig. 2. The lifter devices 110, 210 of such an
alternative
embodiment could be located inside or outside of the gasket 106. If the lifter
devices 110,
210 were located outside of the gasket 106, and, therefore, in direct
communication with
13
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the atmosphere of the lyophilization chamber 16, the tub 102 may not require
the
through-bore 160 and check valve 158 because the reduction in pressure in the
lyophilization chamber 16 would directly act on the lifter devices 110, 210.
[0062] Further, while the foregoing embodiments of the container 100 of the
present
disclosure have thus far been disclosed as including lifter devices 110, 210
with moving
parts, Figs. 6-8 depict an alternative embodiment of a container 300
constructed in
accordance with the principles of the present disclosure including a gasket
306 that serves
as a lifter device 310. Many aspects of the container 300 can be similar to
the aspects of
the container 100 described above, and therefore, like features will be
identified with like
reference numerals.
[0063] Similar to that described above, the container 300 includes a tub 102,
a cover
104, and first through eighth biasing members 108a-108h, only two of which are
depicted
in Fig. 6. The tub 102 of the embodiment of the container 300 is generally
identical to the
tub 102 described above with reference to the container 100 depicted in Figs.
2-4, with
the exception that the container 300 does not include a through-bore 160 or a
check valve
158. The container 300 of Figs. 6-8 can optionally not include these features
because the
lifter device 310, i.e., the gasket 306, is in direct communication with the
ambient
atmosphere of the lyophilization chamber 12, as will be described.
[0064] The gasket 306 of the embodiment of the container 300 of Figs. 6-8 is
disposed
between the cover 104 and the rim 128 of the tub 102 and connected to the rim
128. In
alternative embodiments, the gasket 306 could be connected to the cover 104.
The gasket
306 is of a generally tubular construction such that the gasket 306 itself
includes one
reservoir 350 defining one sealed cavity 352 containing a fluid generally at
atmospheric
pressure. Moreover, the gasket 306 includes a plurality of movable walls 356,
as depicted
in Fig. 8, for example, that serve to move the cover 104 from a closed
position (Fig. 6) to
an opened position (Figs. 7 and 8). In alternative embodiments, the gasket 306
can
include a plurality of tubular portions adjacent the movable walls 356 and
separated by
solid portions. As such, some alternative embodiments of the gasket 306 can
have a
plurality of sealed cavities 352 defined by the plurality of tubular portions.
The movable
walls 356 are spaced apart along the length of the gasket 306. Moreover, the
movable
14
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Docket No. 6702US (31203/45073A/PCT)
walls 356 can include thinned-out resilient sidewall portions of the gasket
306 such that
the movable walls 356 expand when the pressure inside of the sealed cavity 352
exceeds
the ambient pressure surrounding the gasket 306, as shown in Fig. 8.
100651 Accordingly, when undergoing a lyophilization process such as that
described
above, the reduction in pressure within the lyophilization chamber 12 of the
freeze-drying
machine 10 causes the fluid within the scaled cavity 352 of the gasket 306 to
expand,
thereby moving the movable walls 356 away from the remainder of the gasket
306,
which, in turn, moves the cover 104 to the opened position. Because the
movable walls
356 are spaced along the gasket 306, gaps 357 are formed between the gasket
306 and the
cover 104 to allow gas to exhaust out of the tub 102 during lyophilization.
Moreover,
when the ambient pressure within the lyophilization chamber 12 is increased,
the movable
walls 356 return to their normal position depicted in Fig. 6 and the biasing
members
108a-108h urge the cover 104 back to the closed position. With the movable
walls 356 in
the normal position, the gasket 306 provides a fluid tight seal between the
tub 102 and
cover 104.
100661 While the gasket 306 of the embodiment depicted in Figs. 6-8 has been
described as being fixed to the rim 128 of the tub 102 such that the movable
walls 356
move upward against the cover 104 to open the cover 104, in alternative
embodiments,
the gasket 306 could be fixed to the cover 104. For example, the movable walls
356
could be adhered to the cover 104, or the gasket 306, as depicted in Fig. 8
could be
flipped such that the movable walls 356 move downward against the rim 128 of
the tub
102 to open the cover 104.
100671 While each of the foregoing embodiments of the containers 100, 300
includes a
plurality of biasing members 108 connected between the cover 104 and the tub
102 for
returning and maintaining the cover 104 in the closed position, Fig. 9 depicts
one
alternative embodiment of a container 400 that does not include the biasing
members 108.
The container 400 can be generally similar to the container 100 described
above with
reference to Figs. 2-4, and therefore, only the distinctions will be
described. Specifically,
as mentioned, the container 400 does not include the biasing members 108. The
movable
walls 156 of the lifter devices 110, however, are fixed to the cover 104 to
move the cover
CA 02785991 2012-06-26
Docket No. 6702US (31203/45073A/PCT)
104 from the opened position to the closed position, and to maintain the cover
104 in the
closed position when the container 400 is being transported, for example.
[00681 In the disclosed embodiment, the cover 104 is fixed to the movable wall
156 of
each of the lifter devices 110 via a threaded fastener 405. In other
embodiments, the
cover 104 can be fixed to the movable wall 156 of each lifter device 110 with
a snap,
Velcro , an adhesive, or generally any other device. With the container 400 so
configured, the lifter devices 110 move the cover 104 to the opened position
in a manner
identical to that which is described above regarding the container 100
depicted in Figs. 2-
4 when the ambient pressure in the lyophilization chamber 12 is reduced below
the
pressure of the fluid in the sealed cavities 152 of the lifter devices 110.
Upon the ambient
pressure being increased, the fluid in the sealed cavities 152 compresses and
draws the
movable walls 156 downward. Because the movable walls 156 are connected to the
cover 104, this compression of fluid in the lifter devices 110 also pulls the
cover 104 back
into sealing engagement with the tub 102.
[0069] In some embodiments, the pressure of the fluid in the sealed cavities
152 of the
lifter devices 110 can be maintained at a pressure that is actually less than
atmospheric
pressure such that when the container 400 is removed from the lyophilization
chamber 12
and transported, for example, the movable walls 156 of the lifter devices 110
apply a
continuous force pulling the cover 104 downward against the gasket 106 to
maintain a
fluid tight seal. In some embodiments, the pressure of the fluid in the sealed
cavity 152
can be maintained at a pressure that is less than atmospheric pressure, but
greater than the
lowest pressure reached within the lyophilization chamber 12 during the
lyophilization
process, which can be as low as 133 kPa (1 Ton), for example. As such, the
pressure in
the sealed cavities 152 of the lifter devices 110 of this particular
embodiment can be in
the range of approximately 1330 Pa (10 Ton) to approximately 90 kPa (700 Ton),
and in
one embodiment approximately 40 kPa (300 Toff), for example.
f0070] While the concept of connecting the movable walls 156 of the lifter
devices 110
to the cover 104 to eliminate the biasing members 108 has thus far only been
described
with reference to the lifter devices 110 depicted in Figs. 2-4 and 9, this
concept can also
be applied to the lifter devices 210, 310 described above with reference to
Fig. 5 and Figs.
16
CA 02785991 2012-06-26
Docket No. 6702US (31203/45073A/PCT)
6-8. That is, in Fig. 5, the movable wall 258 of the plunger 264 of the
syringe 260 can be
fixed to the cover 104 to eliminate the need for the biasing members 108.
Moreover, the
movable walls 356 of the gasket 306 of Figs. 6-8 could similarly be fixed to
the cover 104
and/or the rim 128 of the tub 102 depending on the orientation of the gasket
306.
[0071] Moreover, while the concept of maintaining the pressure of the fluid in
the
sealed cavities 152 of the lifter devices 110 has only been described with
reference to the
lifter devices 110 depicted in Figs. 2-4 and 9, this concept can also be
applied to the lifter
devices 210, 310 described above with reference to Fig. 5 and Figs. 6-8. That
is, in Fig.
5, the pressure of the fluid in the sealed cavity 252 or within the bellows
268 could be
maintained below atmospheric pressure to apply a constant downward force to
the cover
104. Moreover, the pressure of the fluid in the sealed cavity 352 of the
gasket 306 could
similarly be maintained at a pressure below atmospheric pressure.
[00721 In view of the foregoing, it should be appreciated that the various
embodiments
described herein provide examples of various devices, systems, and methods
constructed
in accordance with the principles of the present disclosure. These embodiments
are not
meant to be exclusive embodiments, but rather, any of the embodiments can be
modified
to include any one or more features of any of the other embodiments. As such,
it should
be appreciated that the examples provided herein are not exhaustive and the
various
features are interchangeable with each other, as well as with features not
specifically
disclosed but understood by a person having ordinary skill in the art.
17
