Note: Descriptions are shown in the official language in which they were submitted.
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ALBUMIN IN A FLEXIBLE POLYMERIC CONTAINER
DESCRIPTION
Technical Field
The present invention relates generally to the packaging of a protein in a
flexible polymeric container, and more specifically to the mass-packaging of
albumin in flexible polymeric containers in an aseptic environment of a fortn
fill-seal packaging machine.
i0
Background of the Invention
Many peptides and proteins for pharmaceutical or other use are known,
including glycoproteins, lipoproteins, iinunoglobulins, monoclonal antibodies,
enzymes, blood proteins, receptor proteins, and hormones.
is One type of such compound is albumin. Albumin is a sulfur-containing,
water-soluble protein that congeals when heated, and occurs in egg white,
milk,
blood, and other animal and vegetable tissues and secretions. Albumin is often
utilized as a blood expander to assist in maintaining a patient's blood
pressure,
or sometimes to assist with increasing a patient's blood pressure during blood
20 loss.
Proteins, such as albumin, are adsorbed by most man-made materials,
including liquid containers made of various polymers. Adsorption of the
protein onto the artificial polymeric surface results in a lowering of the
protein
content of that solution. Some protein solutions can be adversely affected by
25 protein adsorption onto artificial surfaces through a process called
denaturing.
Denaturing is a process whereby the protein is not permanently adsorbed onto
the polymeric container, but rather the protein molecules are adsorbed onto
the
container and then released. The adsorption and release can change the shape
of the molecule (i.e., denature it). Often, when protein molecules in protein
30 drug solutions have undergone denaturing, there may lose their efficacy and
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2
utility. Accordingly, to date proteins such as albumin have been stored for
individual use in glass vials in order to avoid the risk of denaturing.
Because of
the cost encountered in producing, packaging, boxing, shipping and storing
glass vials, as well as the cost and weight of the glass vial, and the ease
with
s which the glass vial may break, a more efficient, inexpensive and user
friendly
means of packaging proteins such as albumin to possibly eliminate the above
drawbacks is desirable.
One type of packaging utilized for packaging non-protein
pharmaceuticals is polymeric bags formed with a form-fill-seal packaging
machine. Form-fill-seal packaging machines are typically utilized to package a
product in a flexible container. The forin-fill-seal packaging machine
provides
an apparatus for packaging certain pharinaceuticals and many other products in
an inexpensive and efficient manner.
Pursuant to FDA requirements, certain pharmaceuticals packaged in
ss form-fill-seal packages are traditionally sterilized in a post-packaging
autoclaving step. The post-packaging step includes placing the sealed package
containing the pharmaceutical in an autoclave and steam sterilizing or heating
the package and its contents to a required temperature, which is often
approximately 250 F, for a prescribed period of time. This sterilization step
operates to kill bacteria and other contaminants found inside the package,
whether on the inner layer of film or within the pharmaceutical itself.
Certain packaged pharmaceuticals, including certain proteins such as
albumin, however, generally cannot be sterilized in such a manner. This is
because the heat required to kill the bacteria in the autoclaving process
destroys
or renders useless certain pharmaceuticals. Further, in the case of albumin
protein, the heat may operate to congeal the protein.
Form-fill-seal packaging may also present other problems beyond
sterilization concerns when packaging certain proteins such as albuinin.
Specifically, conventional form-fill-seal packaging machinery introduces heat
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3
to certain areas of the polymeric material of the package to create seals. If
the heat
contacts the protein during the sealing process, the protein may congeal or
otherwise
denature such as during high-temperature sterilization. Further, since certain
proteins
such as albumin operate as insulators, all seal areas must be free of the
protein in
order for the polymeric materials to be heat sealed together. If any protein
such as
albumin is present in the seal area prior to sealing, the integrity of the
seal may be
jeopardized.
Thus, a convenient and cost-effective means for packaging certain proteins,
including proteins such as albumin is desirable.
Summary of the Invention
The present invention provides a flexible polymeric container for holding a
concentration of peptides and/or proteins. Such peptides and proteins include:
glycoproteins, lipoproteins, imunoglobulins, monoclonal antibodies, enzymes,
blood
proteins, receptor proteins, and hormones. Additionally, the present invention
provides a method of packaging such a compound in a flexible polymeric
container.
Generally, the flexible polymeric container comprises a sheet of flexible
polymeric
film formed into a bag. The bag has a cavity enclosed by a first wall and an
opposing
second wall. The bag further has seals about a periphery of the first and
second walls
that join an interior portion of the opposing first and second walls to create
a fluid-
tight chamber within the cavity of the container. A concentration of the
compound is
stored within the fluid-tight chamber. In one embodiment, the compound is
albumin.
According to one aspect of the present invention, there is provided a flexible
polymeric container for holding a concentrate of water-soluble albumin,
comprising:
a bag made from a sheet of flexible polymeric material initially converted
into a tube with a former, the tube being subsequently converted into a series
of
adjacent bags in an aseptic area of a form-fill-seal packaging machine, the
bags
having a first side member, a second side member peripherally sealed to the
first side
member, and a cavity between an interior of the first and second side members,
wherein a quantity of a concentration of water-soluble albumin is located
within the
cavity of the bag following sequential filling of the albumin into the cavity
of
adjacent bags through an opening of the bags with a filler in the aseptic area
of the
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form-fill-seal packaging machine, the opening of the bags being sealed
sequentially
within the aseptic area of the form-fill-seal packaging machine to create a
fluid-tight
chamber.
According to another aspect of the present invention, the container has a
plurality of peripheral edges. Three of the peripheral edges are sealed with
heat, and
one of the peripheral edges contains a fold that separates the first wall or
first side
member from the opposing second wall or second side member.
According to another aspect of the present invention, a fitment is connected
to the container adjacent the fold. The fitment extends from the outer shell
of the
container at the fold and has a sealed passageway that cooperates with the
fluid-tight
chamber of the container. The sealed passageway extends into the cavity of the
container to allow the albumin to be released from the fluid-tight chamber. A
chevron may be located a distance from the opposing sides of the fitment, and
along
the fold, to assist drainage of the albumin from the container.
According to another aspect of the present invention, the peripheral edge of
the container opposing the fold contains a first seal and a second seal. The
first and
second seals join the first and second opposing walls. An aperture is located
between
the first seal and the second seal, and extends through the first and second
opposing
walls.
According to another aspect of the present invention, the flexible polymeric
sheet material comprises a laminate film having an outside layer of linear low
density
polyethylene, a gas barrier layer, a core layer of polyamide, and an inside
layer of
linear low density polyethylene. The layers are bonded together by a
polyurethane
adhesive.
According to another aspect of the present invention, albumin in
concentrations of 20% and 25% is packaged in the flexible polymeric container.
Additionally, the flexible polymeric containers may have a volume of 50 ml. or
100
ml.
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According to another aspect of the present invention, there is provided a
method of packaging albumin protein comprising the steps of:
providing a flexible polymeric container having an opening extending from a
cavity of the polymeric container,
5 providing a quantity of a concentration of albumin in a sterile solution,
inserting the albumin under a solution line pressure from about 4 psig. to
about 20
psig. into the cavity of the polymeric container through the opening therein;
and
sealing the opening to secure the liquid albumin within a fluid-tight chamber
of the cavity of the polymeric container.
According to another aspect of the present invention, a filler is used to
insert
the albumin into the flexible container. The filler has a distal tip with
adjacent first
and second interior passageways. The first interior passageway has a larger
cross-
sectional area than the second interior passageway. The second interior
passageway
extends adjacent the first interior passageway to an exterior of the tip, and
the
albumin is dispersed from the filler through the second interior passageway.
According to another aspect of the present invention, the interface between
the first and second interior passageways is interior of an exterior of the
tip, and the
second interior passageway extends to the exterior of the tip. The albumin is
maintained at the interface between the first and second interior passageways
during a
suspension of filling of the bags.
According to another aspect of the present invention, a sheath is located
exterior to a portion of the filler adjacent the tip. The sheath prevents
contact
between the polymeric container and the filler.
According to another aspect of the present invention, the sheath is concentric
with the filler. An air passageway extends between an interior of the sheath
and an
exterior of the filler. Further, sterilized air passes through the air
passageway and is
expelled adjacent the tip of the filler and upstream of the albumin exit.
According to another aspect of the present invention, albumin is packaged in
a series of flexible polymeric containers with a form-fill-seal
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packaging machine. A quantity of filtered albumin and a flexible polymeric
material
is provided, and the form-fill-seal packaging machine converts the flexible
polymeric
material into a series of bags. The bags are filled with a quantity of albumin
within
the form-fill-seal packaging machine, and a seal area of the bags is sealed
with the
packaging machine to enclose the quantity of the albumin in the bags.
According to another aspect of the present invention, the adjacent bags in the
series of bags are initially connected, are sequentially filled with a
quantity of
albumin, and are separated following the filling of each bag.
According to another aspect of the present invention, the form-fill-seal
packaging machine has an aseptic area. The sterilized flexible polymeric
material is
provided within the aseptic area, and is formed into bags within the aseptic
area.
Additionally, the filtered albumin is inserted into the bags in the aseptic
area, and the
bags are sealed within the aseptic area to form a fluid-tight container.
According to another aspect of the present invention, albumin is packaged in
a series of flexible polymeric containers in a form-fill-seal packaging
machine with
the following process: converting flexible polymeric material into a tube with
a
former in the form-fill-seal packaging machine; converting the tube into a
series of
bags in the form-fill-seal packaging machine; sequentially filling the bags
with a
quantity of albumin within the form-fill-seal packaging machine; and, sealing
a seal
area of the bags with the packaging machine to enclose the quantity of the
albumin
within the bags. The bags may be filled with a filler that discharges albumin
from the
filler and into the bag without contacting the seal area of the opening of the
bag.
According to yet another aspect of the present invention, there is provided a
process of packaging albumin in a flexible polymeric container, comprising the
steps
of:
providing a concentrate of albumin;
providing a packaging machine having a forming assembly, a filling
assembly, and a sealing assembly, each of which is located within an interior
aseptic
environment of the packaging machine;
providing a flexible polymeric film;
forming the flexible polymeric film into an elongated tube with the forming
assembly;
sealing a portion of the elongated tube of polymeric film with the sealing
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assembly, the sealed polymeric film being dimensioned in the shape of a bag
having
seal areas about a periphery thereof, a cavity located within the bag and
between the
seal areas, and an opening extending from the cavity to an exterior of the
bag;
filling the bag with albumin under a solution line pressure through the
filling
assembly, the filling assembly having a fill tube extending through the
opening of the
bag and into the cavity of the bag, and a sheath concentric to an exterior of
the fill
tube, the fill tube directing the albumin into an interior of the bag a
distance away
from a periphery of the opening of the bag, and the sheath limiting contact
between
the fill tube and the bag; and
sealing the opening of the bag to retain the albumin within the cavity of the
bag.
Accordingly, a flexible polymeric container for storing albumin made in
accordance with the present invention provides an inexpensive, easily
manufactured,
and efficient package and process which eliminates the drawbacks associated
with
prior packages and processes for packaging albumin.
According to yet another aspect of the present invention there is provided a
method of packaging albumin protein in a series of flexible polymeric
containers,
comprising the steps of:
providing a quantity of filtered albumin;
providing a flexible polymeric material;
providing a form-fill-seal packaging machine and converting the flexible
polymeric material into a series of bags in the form-fill-seal packaging
machine;
filling the bags with a quantity of albumin within the form-fill-seal
packaging
machine; and
sealing a seal area of the bags with the packaging machine to enclose the
quantity of the albumin within the bags.
According to yet another aspect of the present invention there is provided a
method of packaging albumin protein in a series of flexible polymeric
containers,
comprising the steps of:
providing a quantity of filtered albumin;
providing a flexible polymeric material;
providing a form-fill-seal packaging machine and converting the flexible
polymeric material into a tube with a former in the form-fill-seal packaging
machine;
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7a
converting the tube into a series of bangs in the form-fill-seal packaging
machine;
filling the bags, through an opening in the bags, with a quantity of albumin
within the form-fill-seal packaging machine; and
sealing a seal area of the opening of the bags with the packaging-machine to
enclose the quantity of the albumin within the bags.
According to still yet another aspect of the present invention there is
provided
a process of packaging albumin in a flexible polymeric container, comprising
the
steps of:
providing a concentrate of albumin;
providing a packaging machine having a filling assembly and a sealing
assembly, the filling and sealing assemblies being located within an interior
aseptic
environment of the packaging machine;
providing a sterile flexible polymeric container having an opening extending
into a cavity;
filling the container with albumin under pressure through the filling assembly
within the aseptic area of the packaging machine, the filling assembly having
a fill
tube exit positioned a distance from a wall of the flexible polymeric
container, the fill
tube exit directing the albumin into the cavity of the container distal the
periphery of
the opening of the container, and the fill tube maintaining the albumin in the
fill tube
a distance from the fill tube exit during filling suspension; and
sealing the opening of the container within the aseptic area of the packaging
machine to retain the albumin within the cavity of the container.
According to still yet another aspect of the present invention there is
provided
a flexible polymeric container filled with albumin, comprising:
an outer shell made of a flexible polymeric sheet material, the material
comprising a laminate film having an outside layer of linear low density
polyethylene
adhesively bonded together with a polyurethane adhesive to a first side of a
polyvinylidene chloride layer, a second side of the polyvinylidene chloride
layer
being adhesively bonded together to a first side of a layer of polyamide, the
second
side of the layer of polyamide being adhesively bonded together with a
polyurethane
adhesive to an inside layer of linear low density polyethylene, the outer
shell having a
first side and an opposing second side heat sealed together at a periphery of
the outer
shell, and a cavity located between the first and second sides, the cavity
forming a
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fluid-tight chamber having a concentration of albumin stored therein, wherein
a
fitment extends from the outer shell, the fitment having a sealed passageway
extending into the cavity of the container to allow the albumin to be released
from the
fluid-tight chamber.
According to still yet another aspect of the present invention there is
provided
a container for holding albumin comprising:
a sheet of flexible polymeric film formed into a bag having a cavity enclosed
by a first wall, an opposing second wall, and seals about a periphery of the
first and
second walls, the seals joining an interior portion of the opposing first and
second
walls and creating a fluid-tight chamber within the cavity of the container,
wherein a
concentration of albumin mixed with a solution of sterile water and
stabilizers is
stored within the fluid-tight chamber.
Other features and advantages of the invention will be apparent from the
following specification taken in conjunction with the following drawings.
Brief Description of the Drawings
To understand the present invention, it will now be described by way of
example, with reference to the accompanying drawings in which:
Figure 1 is a cross-sectional elevation view of a form-fill-seal packaging
machine for manufacturing a flexible polymeric container holding a
concentration of
albumin of the present invention;
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Figure 2 is a schematic view of the process for manufacturing the
flexible polymeric container holding a concentration of albumin of the present
invention;
Figure 3 is a front elevation view of the flexible polymeric container
s holding a concentration of albumin of the present invention;
Figure 4 is a partial side elevation view of the flexible polymeric
container holding a concentration of albumin of Figure 3;
Figure 5 is a side elevation view of a partial filler assembly of the
present invention;
Figure 6 is an enlarged side elevation view of a portion of the filler
assembly of Figure 5;
Figure 7 is a cross-sectional side elevation view of a sheath for the filler
assembly of the present invention;
Figure 8 is an end elevation view of the sheath of Figure 7;
Figure 9 is a schematic cross-sectional view of an embodiment of the
film laminate structure of the present invention; and,
Figure 10 is a cross-sectional view of the end of the fill tube andsheath
of the present invention.
Detailed Description of the Preferred Embodiment
While this invention is susceptible of embodiments in many different
forms, there is shown in the drawings and will herein be described in detail
preferred embodiments of the invention with the understanding that the present
disclosure is to be considered as an exemplification of the principles of the
invention and is not intended to limit the broad aspect of the invention to
the
embodiments illustrated.
As identified above, the breadth of the present disclosure includes the
packaging of any type of certain pharmaceutical compounds such as peptides
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and proteins for pharmaceutical or other use. Such compounds are known and
include: glycoproteins, lipoproteins, imunoglobulins, monoclonal antibodies,
enzymes, blood proteins, receptor proteins, and hormones. For purposes of
example, however, the detailed description of the present invention focuses on
the packaging of albumin in a flexible polymeric container.
Referring now in detail to the Figure 3, there is shown a flexible
polymeric container 12 holding a concentration of albumin of the present
invention. The flexible polymeric container 12 is preferably manufactured by
an aseptic form-fill-seal packaging machine 10 as shown in Figure 1, and
utilizing the process schematically illustrated in Figure 2.
The aseptic form-fill-seal packaging machine 10 generally includes an
unwind section 14, a film sterilizing section 16, a film drying section 18, an
idler roller/dancer roller section 20, a nipped drive roller assembly section
(not
shown), a forming assembly section 22, a fin seal assembly section 24, a
fitment
is attaching assembly section 26, a filling assembly section 30, an end
sealing/cutting assembly section 32, and a delivery section (not shown). Each
of these assemblies downstream of the unwind section 14 is contained within
the internal aseptic environment of the aseptic form-fill-seal packaging
machine
10.
One of the functions of each of the various assemblies of the form-fill-
seal packaging machine 10 is as such: the unwind section 14 contains a roll of
the flexible polyineric film 34 that is ultimately formed into the container;
the
film sterilizing section 16 provides a peroxide bath to sterilize the film 34;
the
film drying section 18 provides a means for drying and cleaning the peroxide
from the film 34; the forming assembly 22 provides a forming mandrel 36 to
convert the web of film into a tube 38 that ultimately becomes the flexible
container or bag 12; the fin seal assembly 24 provides the longitudinal seal
40
on the tube 38 that ultimately becomes the longitudinal seal 40 on the
flexible
container 12, thereby longitudinally sealing the forined tube 38; the fitment
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attachment assembly 26 attaches a fitment 42 to the tube 38; the filling
assembly 30 includes a filler 44 that fills the flexible containers 12 with a
substance, that being a concentration of water-soluble albumin in the present
preferred application; and, the end sealing/cutting assembly 32 contains
cutting
5 and sealing jaws 46 that form the end seals 76,78 of the flexible polymeric
containers 12 to enclose the albumin within the flexible polymeric container
12.
In the preferred embodiment, the albumin utilized to be packaged in the
flexible polymeric container 12 is either a 20% human albumin or a 25% human
albumin. To achieve the required concentration level, the albumin is typically
10 combined with sterile water and stabilizers. Further, prior to packaging
the
albumin concentration is pasteurized and stored in large stainless steel
holding
tanks (not shown) having a volumetric capacity of approximately 500-600
liters, at approximately 2 C to 8 C. Immediately before packaging, the albumin
tanks are removed from refrigeration and allowed to equilibrate to the
is packaging room temperature (approximately 68 F). It is important to process
albumin at temperatures which do not result in denaturing of the protein,
approximately below 60 C. However, anywhere between 0 C and 60 C, and
more preferably between 20 C and 45 C is appropriate. Additionally, in one
embodiment the process temperatures 68 F to 77 F. Additionally, the albumin
is filtered through a 0.2 micron filter as it enters the packaging machine 10.
The flexible polymeric film 34 utilized in the preferred embodiment of
the present invention is a linear low density polyethylene laminate. It has
been
found that such a film with a gas barrier is particularly suitable for housing
oxygen labile solutions, such as the identified proteins, including albumin.
Specifically, it has been found that this film reduces or eliminates the
denaturing process previously associated with placing proteins, such as
albumin, in a plastic container. As shown in Figure 9, in the preferred
embodiment the laminate film 34 has an outside layer of linear low density
polyethylene (LLDPE) 52, a gas barrier layer 54, a core layer of polyamide 56,
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and an inside layer of linear low density,polyethylene 58, the layers being
bonded together by a polyurethane adhesive 60. Most preferably, the material
requirements of the laminate structure has the following charaeteristics: a
LLDPE layer (approximately 61 f 10 pm) 52, a polyurethane adhesive layer 60,
a polyvinylidene chloride (PVDC) layer (approximately 19 f 5 Eim) 54, a
polyurethane adhesive layer 60, a nylon layer (approximately 15 :~ 5 fan) 56,
a
polyurethane adhesive layer 60, and LLDPE layer (approximately 61 f 10 Om)
52. In total, the thickness of the film is approximately 160 f 25 X.
Additionally, the PVDC layer 54 is most preferably manufactured by Dow
Chemical and sold under the t-ademark SARAN. Such a fihn is disclosed in
U.S. Patent No. 4,629,361. U.S. Patent No. 4,629,361 is assigned to the
assignee of the present invention. This film 34 is manufactured by Fujimori
under
the trade name FTR-13F.
Prior to usage, the internal aseptic area of the packaging machine must
be sterilized each day. This is accomplished with a hydrogen peroxide fog
which is passed through the aseptic atea of the packaging machine.
As seen in Figure 1, the roll of film 34 is located in the unwind section
14 of the packaging machine 10. During use, the film 34 is transferred through
a hydrogen peroxide bath 16 to sterilize the film before entering the aseptic
area
of the packaging machine 10. This sterilization step cleans the web of film so
-
that it can be utilized to create a sterile product. Sterilization and
cleansing of
the film is critical in the medical industry when one is packaging parenternal
or
enteral products. This sterilization step is especially critical when the
resultant
product is not to be terminally sterilized, i.e., when the packaging machine
is an
aseptic packaging machine. After the film has been washed, cleaned or
sterilized, liquid and other residue, for example the chemical sterilant or
wetting
agent such as the hydrogen peroxide typically remains on the fihn. Thus, it is
necessary to remove the liquid and/or residue from the film 34. An air lmife
(a
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stream of air blown across the web of film so that the liquid contained
thereon
is blown off the film) located in the film drying section 18 is utilized to
remove
liquid and other residue from the film 34 as the film enters the aseptic area
of
the packaging machine.
In the aseptic area of the packaging machine 10, the film 34 passes
through the dancer roller section 20 and the drive roller section prior to
entering
the forming assembly section 22. Before entering the forming assembly 22 the
web of film 34 is substantially planar, and has a first surface 62 and a
second
surface 64. The first surface 62 faces downward as the film enters the forming
assembly 22 and ultimately becomes an interior of the container 12, while the
second surface 64 faces upward as the film enters the forming assembly 22 and
ultimately becomes the outside of the container 12.
As shown in Figures 3 and 4, the film 34 additionally has a tlieoretical
fold-line approximately located about a centerline of the length of the web of
film 34. The theoretical fold-line becomes a fold area 67 that separates the
first
side member 66 or first wall from the second side member 68 or second wall of
the container 12.
A forming mandrel 36 is located in the forming assembly section 22.
The forining mandre136 assists in converting the substantially planar web of
polymeric material 34 into an elongated and substantially tubular member 38.
It is understood that the elongated tubular member 38, or tube, is generally
not
cylindrical, but rather has an oblong shape as shown in Figure 4. In
connection
with the identification of the areas of the web of film as described above,
after
the film 34 traverses through the forming assembly 22, the first surface 62 of
the first side member 66 opposes the first surface 62 of the second side
member
68.
Once the tubular member 38 is formed, the tubular member receives a
longitudinal seal 40 in the fin seal assembly section 24, and a fitment 42 is
connected to the tube 38 in the fitment attachment assembly 26. Specifically,
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fitment 42 is attached to and extends from the outer shell of the container 12
at
the fold area 67 with the use of a heated assembly to seal the fitment 42 to
the
fold area 67 of the container 12. Typically, the fitment sealer operates at a
temperature from about 415 F to about 450 F, and with a pressure from about
55 psig to about 70 psig, although any range within these identified ranges is
acceptable. As shown in Figure 4, the fitment 42 has a sealed passageway that
cooperates with the interior of the tube 38. Specifically, the passageway
extends into and creates a fluid communication with the cavity 82 of the
container to allow the albumin to be released from the fluid-tight chamber. It
io should be understood that in some embodiments the albumin may be injected
into the cavity 82 of the container 12 through the fitment 42.
The fin seal assembly 24 introduces heat and pressure to the film 34 to
create the longitudinal seal 40 at the peripheral edge of the tube 38 that
opposes
the fold area 67. Typically, the fin seal assembly operates at a temperature
from
.is about 350 F to about 380 F, and with a pressure from about 40 psig to
about 80
psig, although any range within these identified ranges is acceptable In the
preferred embodiment of the container 12 as shown in Figure 3, the
longitudinal
seal 40 comprises a first longitudinal seal 70 and a second longitudinal seal
72.
The first and second longitudinal seals 70,72 join the first surface 62 of the
first
20 wal166 to the opposing first surface 62 of the second wal168. An aperture
74,
typically utilized to hang a formed container 12, is created between the first
longitudinal seal 70 and the second longitudinal seal 72. Accordingly, the
aperture 74 extends through the first and second opposing walls 66,68.
The sealed tubular member 38 traverses from the fin seal assembly 24 to
25 the filling assembly 30 and the end sealing assembly 32. At the end sealing
assembly 32, the form-fill-seal packaging machine 10 utilizes heat and
pressure
to convert the sealed tube 38 into a series of bags 12, also referred to as
containers 12. Typically, the end sealing assembly operates at a temperature
from about 375 F to about 405 F, and with a pressure from about 500 psig to
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about 850 psig, although any range within these identified ranges is
acceptable.
The sealed tube 38 first receives a bottom seal 76 to initially form the bag
12
having a cavity 82 located between the first and second sides 66,68 of the
container 12 and the bottom seal 76 of the container, and an opening 80 that
s extends from the cavity 82 of the container 12 to an exterior of the
container 12.
It should be understood that during the form-fill-seal manufacturing process,
the
opening 80 extends from the cavity 82 of the container 12 into the center of
the
tube 38. Once the bottom seal 76 is created, the bag 12 is filled with the
albumin through the opening 80, and then the top seal 78 is formed, thus
sealing
or closing the opening 80 and creating a fluid-tight chamber 82 wherein the
albumin is retained. Further, once the bottom seal 76 is created, the
polymeric
film 34 can be said to be dimensioned in the shape of the open bag 12, having
seal areas about its periphery (the longitudinal seal 34 opposing the fold
area
67, and the bottom seal 76 joining the fold area 67 and the longitudinal
sea140),
i5 and having a cavity 82 located within the bag 12 and between the seal areas
40,
76 and the fold area 67. Thus, with a form-fill-seal packaging process, the
finished container 12 has sealed areas on three sides of the bag 12: the top
seal
78, the bottom sea176, and the longitudinal seal 40. The longitudinal seal 40
joins the top seal 78 and the bottom seal 76. In the preferred process, the
top
seal 78 of a first bag 12 is formed at the same time as the bottom seal 76 of
an
adjacent upstream bag 12 with the end sealing assembly 32. As such, adjacent
bags 12 in the series of bags 12 are initially connected, both by being part
of the
tubular member 38 that forms the bags 12, as well as by having end seals that
are formed with the same end sealing assembly 32.
In the preferred embodiment of the process for creating and filling
containers of present invention with albumin as illustrated in Figures 1 and
2,
the containers 12 are filled with the albumin through a filling assembly 30
that
extends down the tube 38. The filling assembly 30 thus fills the cavity 82 of
the
bag 12 through the opening 80 of the in-process three-sided and open bag 12.
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The filling assembly 30 of the preferred embodiment is illustrated in
Figures 5-8 and 10. As such, the filling assembly 30 comprises a pressurized
filler 44 made up of a fill tube 84, and a sheath 86 located concentrically
about
the perimeter of the fill tube 84. The filler 44 typically operates under a
5 solution line pressure of from about 4 psig. to about 20 psig, however, any
range of pressures within the identified range is acceptable. In the preferred
embodiment, the filler operates under a solution line pressure of from about
10
psig. to about 16 psig, and most preferably under a solution line pressure of
from about 12 psig. to about 16 psig. The identified ranges are utilized in an
10 attempt to reduce turbulence and splashing of the albumin or other protein
as it
is inserted into the container 12. As explained above, after the bottom seal
76 is
created, the bag 12 is filled with the albumin through the filling assembly
30,
the top sea178 is created simultaneously with the bottom sea176 of the next
bag, the next bag 12 of the tube 38 is sequentially filled, and so on and so
forth.
15 Thus, adjacent bags 12 in the series of bags 12 are initially connected,
and are
then separated following sequentially filling and sealing of each respective
bag
12.
As shown in Figure 5, in the preferred embodiment, the filler 44 of the
filling assembly 30 is configured as a tube 86 overa tube 84. The sheath tube
86 is situated concentric about the fill tube 84, with an air passageway 88
extending in the space between the inner diameter of the sheath tube 86 and
the
outer diameter of the fill tube 84. Sterilized air passes through the air
passageway and is expelled adjacent a tip of the fill tube 84, upstream of a
fill
tube exit 92.
In a preferred embodiment of the fill tube 84 as shown in Figure 5, the
fill tube 84 has a venturi 85 in that it tapers from a first diameter to a
second
larger diameter about its length. Further, as shown in Figure 6, the tip 90 of
the
fill tube 84 has a first interior passageway 94 concentric with and adjacent a
second interior passageway 96. And, in a preferred embodiment of the present
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16
invention, the first interior passageway 94 is generally circular in cross-
sectional shape, having a first interior diameter, and the second interior
passageway 96 is generally circular in cross-sectional shape, having a second
interior diameter. The interior diameter, and thus the cross-sectional area of
the
first interior passageway 94 is dimensioned larger than the interior diameter,
and thus the cross-sectional area of the second interior passageway 96. An
interface 98 connects the first interior passageway 94 and the second interior
passageway 96 at a location that is interior of an exterior of exit 92 of the
tip 90
of the filler 44. In a preferred embodiment, the interface comprises a
chamfered
io step 98 between the first and second interior passageways 94,96 to sharply
reduce the diameter from the first interior passageway 94 to the second
interior
passageway 96. The interface 98 between the first and second passageways
94,96 provides a impoi-tant function in the operation of the filler. Since the
albumin is dispensed from the exit of the second interior passageway 96 of the
is filler 44, capillary forces in the fill tube operates to have the meniscus
of the
albumin reside at the interface 98 between the first and second passageways
94,96 during a stoppage in filling instead of at the exit 92 of the second
passageway. Thus, even though the albumin is dispersed from the filler 44
through the second interior passageway 96, during each suspension in filling
in
20 between sequential filling of the bags 12, the albumin is maintained
interior to
and a distance from the exit of the filler 44, and at the interface 98 of the
first
and second passageways 94,96. Such a configuration greatly assists in
preventing migration of the albumin from the exit of the filler. Any migration
may allow the albumin to be transferred onto an exterior of the filler and
contact
25 the film 34. As explained above, albumin operates as an insulator. If the
albumin migrated onto the film it would likely jeopardize the integrity of the
top seal area. Thus, the configuration of the present invention provides a
means
for eliminating this drawback. In testing conducted on the seal integrity of
the
containers 12 of the present invention, 99.90% of the formed containers 12
were
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17
above the minimum seal strength value of 20 psi in burst test evaluation.
As explained above, the sheath 86 resides concentrically about a
perimeter of the fill tube 84, and an air passageway 88 extends in the space
between the inner diameter of the sheath tube 86 and the outer diameter of the
s fill tube 84. While in the preferred embodiment the distal end portion 100
of
the sheath 86 is an adapter that is mounted on the sheath 86, the distal end
portion 100 may be manufactured as part of the sheath 86 without destroying
the intended function of the sheath 86. As shown in Figures 7 and 8, the
distal
end portion 100 of the sheath 86 has a chamfered end 104. A plurality of vent
3.0 holes 102 are located adjacent the end of the distal end portion 100 of
the sheath
86. The sterilized air is dispelled from the air passageway 88 out of the vent
holes 102. Since the exit of the vent holes 102 resides at the chamfered end
104
of the sheath 86, the flow pattern of the sterilized air is circumferentially
exterior to the flow pattern of the albuinin being dispelled from the fill tip
so as
is not to interfere with the flow of the albumin. This decreases the chances
of the
sterilized air from introducing a turbulent effect to the dispensed albumin.
Additionally, since the air flow pattern is exterior to and away from the
liquid
flow pattern of the albumin, any possible foaming of the albumin that may
come in contact with the air is minimized. Similar to the benefits uncovered
20 with the dual inner diameters of the fill tube 84, the benefits uncovered
with the
flow of the sterilized air are extremely useful. Such a configuration greatly
assists in preventing splashing and foaming of the albumin from the exit of
the
filler. This, prevents contact by the albumin with the portion of the film
that is
converted into the top seal area, thereby also aiding in continually creating
a
25 stronger top seal.
The first interior diameter 106 of the distal end portion 100 of the sheath
86 is dimensioned to fit onto the sheath 86 and be secured thereto with a
setscrew 110. The second interior diameter 108 of the distal end portion 100
of
the sheath 86 is dimensioned to provide the air passageway 88 between the
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sheath 86 and the fill tube 84. As shown in Figure 7, a chamfer 112 is located
at the end of the second interior diameter 108 to furtlier reduce the inside
diameter of the sheath 86. A reverse chamfer 114 is located at an exterior
portion of the end of the sheath 86.
The sheath 86 and fill tube 84 are shown as assembled in Figure 10. As
seen in the illustration, the outside diameter of the fill tube 84 is
dimensioned to
be the same as or slightly less than the reduced inside diameter of the sheath
86
at the chamfer 112. In the preferred embodiment, the second interior diameter
of the sheath 86 is approximately 0.584 inch, and is decreased at the chamfer
112 to approximately 0.500 inch. Additionally, the outside diameter of the
fill
tube 84 of the preferred embodiment of the present invention is approximately
0.500 inch. As such, interface between the chamfer 112 and the fill tube 86
operates to close the air passageway 88 and force the sterilized air out the
vent
holes 102 located upstream of the exit 92 of the second interior passageway of
is albumin fill tube 84.
As seen in Figure 10, the outside diameter of the sheath 86 is larger than
the outside diameter of the fill tube 84 protruding past the sheath 86. Often
during filling the tube 38 of film contacts the filling assembly 30. With the
identified configuration of the fill tube and sheath, even though during a
portion
of the filling process the fill tube 84 of the filling assembly 30 extends
through
the opening 80 of the bag and into the cavity 82 of the bag, the sheath 86 is
exterior to a portion of the fill tube 84, and thus only the sheath 86 can
contact
the tube 38, thereby preventing contact between the polyineric container and
the
fill tube 84. As such, the exit 92 of the fill tube 84 is positioned a
distance away
from the interior wall of the flexible polymeric container 12. - Thus, the
position
and size of the sheath 86 in combination with the interior interface 98 of the
first and second interior passageways, and the reverse chamfer 114 prevents
any
albumin from migrating to an exterior of the filling assembly 30 and coming in
contact with the seal areas of the tube 38 that ultimately become the top seal
78
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of the finished container. Since albumin operates as an insulator, it is
necessary
to maintain all seal areas free of the protein in order for the polymeric
materials
to be heat sealed together. If any albumin was present in the seal area prior
to
sealing, the integrity of the seal may be jeopardized. As such, with the
s identified configuration, the albumin is discharged from the fill tube 84
and into
the bottom of the bag 12 without contacting the seal area of the opening of
the
bag 12 that ultimately becomes the top seal 78.
While the specific embodiments have been illustrated and described,
numerous modifications come to mind without significantly departing from the
spirit of the invention, and the scope of protection is only limited by the
scope
of the accompanying Claims.
