U.S. patent application number 13/499738 was filed with the patent office on 2012-08-02 for production of a biopharmaceutical product.
This patent application is currently assigned to SARTORIUS STEDIM BIOTECH S.A.. Invention is credited to Magali Barbaroux, Samuel Dorey, Mareva Gueneron, Oscar Reif.
Application Number | 20120193264 13/499738 |
Document ID | / |
Family ID | 42274539 |
Filed Date | 2012-08-02 |
United States Patent
Application |
20120193264 |
Kind Code |
A1 |
Barbaroux; Magali ; et
al. |
August 2, 2012 |
PRODUCTION OF A BIOPHARMACEUTICAL PRODUCT
Abstract
Process of producing a biopharmaceutical product includes
providing a pouch unit including a pouch and at least one port, and
optionally, a functional device; filling the pouch with the
product; carrying out the production process, and at at least one
stage thereof, using or generating a liquid or small solid incident
body within the biopharmaceutical product; the pouch unit
incorporating a support and replacement element formed by or
integrated in the pouch wall, or in the port or functional device
so as to be accessible from the inside space and be in direct
physical contact with the contents of the pouch, arranged so as to
be able to be loaded with the incident body and pass between the
support and replacement element and the contents, such that the
incident body is loaded on the support and replacement element when
it is not or should not be within the biopharmaceutical
product.
Inventors: |
Barbaroux; Magali; (La
Destrousse, FR) ; Dorey; Samuel; (Auriol, FR)
; Gueneron; Mareva; (Auriol, FR) ; Reif;
Oscar; (Hannover, DE) |
Assignee: |
SARTORIUS STEDIM BIOTECH
S.A.
AUBAGNE
FR
|
Family ID: |
42274539 |
Appl. No.: |
13/499738 |
Filed: |
September 29, 2010 |
PCT Filed: |
September 29, 2010 |
PCT NO: |
PCT/FR10/52048 |
371 Date: |
April 2, 2012 |
Current U.S.
Class: |
206/524.1 ;
53/467 |
Current CPC
Class: |
C12M 29/00 20130101;
C12M 29/04 20130101; C12M 23/14 20130101 |
Class at
Publication: |
206/524.1 ;
53/467 |
International
Class: |
B65D 85/84 20060101
B65D085/84; B65B 1/04 20060101 B65B001/04 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 2, 2009 |
FR |
0956889 |
Claims
1-27. (canceled)
28. Process for the production of a biopharmaceutical product in
substantially liquid or paste form by a
physical-chemical-biological production process, in which: A pouch
unit (1) is provided that includes a pouch (2) that defines an
inside space (2a) that can contain the biopharmaceutical product
during its production process, and said pouch unit is limited by a
continuous wall (3) that is flexible, airtight, and non-degradable,
and that can be in direct contact by its inside face (3b) with the
biopharmaceutical product and can contain it, and, combined with
the pouch (2), at least one port (4), and, if necessary, at least
one functional device (5), The biopharmaceutical product that is
not totally finished or components of the latter is/are provided,
and the pouch (2) is filled with said product or components, thus
constituting the contents of the pouch (2), The process for
production is implemented in and with the pouch unit (1), and
during this process, at least one incident body that is solid and
small in size or liquid that is within the biopharmaceutical
product is used or generated at at least one time or stage of the
production process, characterized by the fact that: The at least
one incident body that is solid and that is broken into a number,
more specially a large number, of units or pieces of a dimension on
the order of, or less than, or significantly less than, a
millimeter, down to molecular size, is generated, A pouch unit (1)
that is selected for incorporating an inherent means of support and
replacement (6) is provided: Formed by or integrated in the wall
(3) of the pouch (2) or in at least one port (4) or functional
device (5), in such a way as to be able to be accessible from the
inside space (2a) of the pouch (2) and in direct physical contact
with the contents of the pouch (2), Arranged in such a way as to be
functionally able to be loaded with the incident body and to make
possible the passage of the incident body between one and the other
of the inherent means of support and replacement (6) and within the
contents of the pouch (2), Being functionally active per se or as a
consequence of a dedicated activation operation, The pouch unit (1)
is used in such a way that the inherent means of support and
replacement (6) is in direct physical contact with the contents of
the pouch (2) and in such a way that with the inherent means of
support and replacement (6) being functionally active, the incident
body passes substantially between one and the other of the inherent
means of support and replacement (6) and within the contents of the
pouch (2) in such a way that the incident body is substantially
loaded on the inherent means of support and replacement (6) when it
is not or should not be substantially within the biopharmaceutical
product.
29. Process according to claim 28, wherein the inherent means of
support and replacement (6) is functionally active in response to
the value taken on by at least one physical-biological-chemical
condition of the contents of the pouch (2) or in response to the
value taken on by the variation of such a
physical-biological-chemical condition or in response to a
dedicated activation operation of a physical, biological, or
chemical nature.
30. Process according to claim 28, wherein once the
biopharmaceutical product has been produced and is in the pouch
(2), the inherent means of support and replacement (6) is
substantially loaded with the incident body, whereas before filling
with contents, the inherent means of support and replacement (6) is
not loaded with the incident body.
31. Process according to claim 28, wherein before filling with
contents, the inherent means of support and replacement (6) is
substantially loaded with the incident body, whereas once the
biopharmaceutical product has been produced and is in the pouch
(2), the inherent means of support and replacement (6) is not
loaded with the incident body.
32. Pouch unit (1) that is specially designed for the
implementation of the process for the production of a
biopharmaceutical product in substantially liquid or paste form
according to claim 28, including a pouch (2) that defines an inside
space (2a) that can contain the biopharmaceutical product during
its production process, limited by a continuous wall (3) that is
flexible, airtight, and non-degradable, and that can be in direct
contact by its inside face (3b) with the biopharmaceutical product
and can contain it, and, combined with the pouch (2), at least one
port (4), and if necessary at least one functional device (5),
which: Incorporates an inherent means of support and replacement
(6): Formed by or integrated in the wall (3) of the pouch (2) or in
at least one port (4) or functional device (5), in such a way as to
be able to be accessible from the inside space (2a) of the pouch
(2) and in direct physical contact with the contents of the pouch
(2), Arranged in such a way as to be functionally able to be loaded
with the incident body and to make possible the passage of the
incident body between one and the other of the inherent means of
support and replacement (6) and within the contents of the pouch
(2) itself, Functionally active per se or as a consequence of a
dedicated activation operation, Is implemented such that the
inherent means of support and replacement (6) is in direct physical
contact with the contents of the pouch (2) and such that, with the
inherent means of support and replacement (6) being functionally
active, the incident body passes substantially between one and the
other of the inherent means of support and replacement (6) and
within the contents of the pouch (2) itself, and is substantially
loaded on the inherent means of support and replacement (6) when it
is not or should not be substantially within the biopharmaceutical
product.
33. Pouch unit (1) according to claim 32, wherein the inherent
means of support and replacement (6) consists of or comprises a
membrane or a coating or a surface treatment of the wall (3) of the
pouch (2) or at least one port (4) or functional device (5), or a
body of support and replacement, or a compartment of support and
replacement.
34. Pouch unit (1) according to claim 32, wherein the inherent
means of support and replacement (6) is located toward the inside
face (3b) of the wall (3) of the pouch (2) or at least one port (4)
or functional device (5) that forms it or integrates it.
35. Pouch unit (1) according to claim 32, wherein the inherent
means of support and replacement (6) is located over the entire
surface or on only one portion of the surface of a face of the
pouch (2) or at least one port (4) or functional device (5) that
forms it or integrates it by then being either located or
distributed over this face.
36. Pouch unit (1) according to claim 32, that has, during the
process for the production of the biopharmaceutical product, a
lower part (2b), an upper part (2c), and a median part (2d),
wherein the inherent means of support and replacement (6) is
located at least in the lower part (2b) or at least in the lower
part (2b) and in all or part of the median part (2d) of the pouch
unit (1).
37. Pouch unit (1) according to claim 32, characterized by an
inherent means of support and replacement (6) that has a surface
area for replacement with the contents of the pouch (2) during the
process for the production of the biopharmaceutical product that is
larger than, more specially significantly larger than, more
specially on the order of a multiple of, the surface area of the
inside face (3b) of the wall (3) of the pouch (2) or at least one
port (4) or functional device (5) that forms it or integrates it,
and that is in direct contact with the contents of the pouch (2),
as a result of the composition of the inherent means of support and
replacement (6), or the wall (3) of the pouch (2) or at least one
port (4) or functional device (5) that forms it or in which it is
integrated or the configuration of the inherent means of support
and replacement (6) on the wall (3) of the pouch (2) or at least
one port (4) or functional device (5) that forms it or in which it
is integrated.
38. Pouch unit (1) according to claim 32, wherein the inherent
means of support and replacement (6) is functionally active in
response to the value taken on by at least one
physical-biological-chemical condition of the contents of the pouch
(2) or in response to the value taken on by the variation of such a
physical-biological-chemical condition or in response to a
dedicated activation operation of a physical, biological, or
chemical nature.
39. Pouch unit (1) according to claim 32, wherein the pouch (2) is
either a 2D pouch or a 3D pouch.
40. Pouch unit (1) according to claim 32 before filling with
contents, wherein the inherent means of support and replacement (6)
is not loaded with the incident body.
41. Pouch unit (1) according to claim 32 before filling with
contents, wherein the inherent means of support and replacement (6)
is substantially loaded with the incident body.
42. Pouch unit (1) according to claim 32 that is filled with
finished biopharmaceutical product, wherein the inherent means of
support and replacement (6) is not loaded with the incident
body.
43. Pouch unit (1) according to claim 32 that is filled with
finished biopharmaceutical product, wherein the inherent means of
support and replacement (6) is substantially loaded with the
incident body.
44. Unit that comprises, in the first place, a pouch unit (1)
according to claim 32, wherein the inherent means of support and
replacement (6) is functionally active as a consequence of a
dedicated activation operation, and, in the second place, means of
activation of the inherent means of support and replacement (6) of
a physical, biological or chemical nature.
45. Unit according to claim 44, wherein the activation means either
consist of the biopharmaceutical product P that is in the inside
space (2a) of the pouch unit (1) and that has properties that can
activate the inherent means of support and replacement (6) or are
located outside of the pouch unit (1).
Description
[0001] The invention relates to the production of a
biopharmaceutical product, and its purpose is more particularly a
process for the production of a biopharmaceutical product in and
with a pouch unit that is selected for this purpose, such a pouch
unit being specially designed for implementing this process, such a
pouch unit before the filling of contents, and such a pouch unit
that is filled with the finished biopharmaceutical product, and,
finally, a unit that comprises, in the first place, a pouch unit,
and, in the second place, means for activation of the inherent
means of support and replacement of the pouch unit.
[0002] "Biopharmaceutical product" is defined as a product that is
obtained from biotechnology--culture media, cellular cultures,
buffer solutions, artificial nutrition liquids, blood products and
derivatives of blood products--or a pharmaceutical product, or more
generally a product that is designed to be used in the medical
field. In the context of the invention, this biopharmaceutical
product has the characteristic of being in a substantially liquid
or paste form.
[0003] For the purposes of production of such a biopharmaceutical
product, it is common to place it directly in a pouch that is part
of a device that is designed for its production. Such a device
first of all comprises a pouch unit that includes, in the first
place, the pouch in question itself, defining an inside space that
can contain the biopharmaceutical product, limited by a wall,
continuous as a whole, made of a film of flexible plastic material
that is airtight, and non-degradable, and that can be in direct
contact by its inside face with the biopharmaceutical product, and
can contain it, and, in the second place, combined with the pouch,
at least one port, and, if necessary, at least one functional
device such as a device for mixing, aeration, . . . . Such a device
can next comprise, if necessary, an outside rigid container for
receiving the pouch unit in its inherent inside space.
[0004] "Production process" is defined as one or more phases of a
physical-chemical-biological process during which the
biopharmaceutical product is partly or completely manufactured to
reach the finished state that allows its immediate use or a
semi-finished state that allows a subsequent use. Such a phase
consists in, for example, the addition of one or more components
using at least one port of the pouch unit, or in a mixture, an
aeration, a filtration, a reaction, a heating or a cooling (with
this list not being exhaustive), using at least one suitable
functional device with which the pouch unit is provided.
"Biopharmaceutical product" is defined both as the
biopharmaceutical product in the finished state and an intermediate
product of the process for producing the latter.
[0005] A pouch unit that has a pouch whose two large walls are
directly joined to one another is known. Once expanded, such a
pouch has a limited volume and remains relatively thin, which
justifies the fact that this pouch is often called "pillow" pouch
or "2D" pouch (with D meaning dimensions). A 3D pouch with gussets
that comprises two end walls and one side wall that can be folded
flat or deployed unfolded, welded to one another, with the volume
then able to be at least 50 liters, up to 3,000 liters, and even
more, is also known. Such a 3D pouch is described in the document
WO00/04131 or is marketed by the company Sartorius Stedim Biotech
under the trademark FLEXEL.RTM. 3D.
[0006] With such a pouch unit, the wall of the pouch performs a
unique mechanical function that consists in, on the one hand,
containing the substantially liquid or pasty biopharmaceutical
product by absorbing the forces that result from its presence in
the inside space of the pouch and its direct contact with its
inside face, and, on the other hand, to support the at least one
port and, if necessary, the at least one functional device.
[0007] The production of the biopharmaceutical product in the pouch
unit uses or generates one or more bodies that are functionally
intrinsic to the biopharmaceutical product within the scope of its
production, i.e., being part of the biopharmaceutical product or a
component of the latter or used for the production of the
biopharmaceutical product or generated upon this occasion. Such a
body is qualified here as an incident body.
[0008] Such an incident body is such that: [0009] At one or more
times or in one or more stages of the process for the production of
the biopharmaceutical product, it is necessarily substantially
within the substantially liquid or pasty biopharmaceutical product,
[0010] And at one or more other times or in one or more other
stages of the production process, it is not or should not be
substantially within the biopharmaceutical product.
[0011] Being and not being "substantially" within the
biopharmaceutical product means, respectively, in a very
predominant and quantitatively prominent way, that the incident
body is located and is not located within the biopharmaceutical
product.
[0012] Such a body is termed incident relative to the
biopharmaceutical product, because it is necessary to understand
that the weight and the volume of the body are low to very low and
even minute relative to the weight and the volume of the
biopharmaceutical product.
[0013] Such a body is solid and small in size or liquid (including
paste form); in any case, it is not gaseous. "Solid" is defined as
the fact of exhibiting a certain cohesion or a certain consistency
and being neither liquid nor gaseous. A toxin or a microorganism is
part of the definition of solid. "Small in size" is defined as a
dimension on the order of, or less than, or significantly less
than, a millimeter, down to molecular size.
[0014] Such a body, if it is solid, is individual or broken into a
number, more specially a large number, of units or pieces. This is
why, even though such a body is solid, it is possible to describe a
biopharmaceutical product that contains it within itself as being
in a substantially liquid or paste form. Consequently, a
biopharmaceutical product that is in a "substantially" liquid or
paste form means, in a very predominant and quantitatively
prominent way, that the biopharmaceutical product is in liquid or
paste form, even when it comprises such a solid body within
itself.
[0015] Such an incident body can be varied, concerning its
substance, its nature, its structure, its composition, its
function, its origin, its properties, its usefulness or its
harmfulness . . . . It may involve, for example, a body that falls
within the final composition of the biopharmaceutical product or
falls within its initial composition or active ingredients or
wastes or reaction by-products or impurities or a catalyst,
activator, regulator or a toxin or an antibiotic or a body that
acts on one or more physical-biological-chemical conditions of the
biopharmaceutical product or one or more
physical-biological-chemical conditions that prevail(s) in the
pouch or antibody, cells, or bacteria.
[0016] With a pouch unit for the production of biopharmaceutical
products as known today, there is an obligation to abstract such an
incident body, which is not always desirable or possible, or to
implement an exogenic means with the pouch unit--structural or
functional--which is suitable for this body. For example, the
following are provided: a stage and the device for introduction
into the pouch that is filled with biopharmaceutical product--or
components of such a product or else intermediate products of such
a final product--of such a body such as a nutrient, antibiotic,
active substances, catalyst and/or a stage and the device for
evacuating the pouch that is filled with biopharmaceutical
product--or components of such a product or else intermediate
products of such a final product--of such a body such as an
undesirable or toxic substance. Such a device for introduction or
evacuation is, for example, a port that can be closed or open based
on the requirements.
[0017] "Patches" that are designed to be applied on the skin of an
individual comprising one or more active substances that are
released once the patch is applied to the skin for dermal or
transdermal use are known. Reference can be made to, for example,
the documents EP-A-0278473, U.S. Pat. No. 4,557,723, U.S. Pat. No.
4,638,043, U.S. Pat. No. 4,752,478 and US-A-2009/0142388.
[0018] Oxygen absorbers (oxygen scavengers) that are designed quite
specially for the packaging of food products for the purpose of
limiting or preventing their oxidation and thus to allow a more
significant preservation period are known. Such an oxygen absorber
can come in the form of a packet or a pellet or a label that is
introduced into the packaging beside the food product or can be
included or combined with the wall of the packaging itself. It is
possible to refer to, for example, the documents WO 2008/084231 and
WO 2005/033676. In the same way, moisture absorbers, corrosion
inhibitors, absorbers of bad odors, gas emitters, and antibacterial
agents are known.
[0019] Such devices are well suited to their own purpose but cannot
be applied in the case of the production of a biopharmaceutical
product, as it was defined above, in particular because the product
concerned is in solid form and not in liquid or paste form, and/or
because the purpose of the device is the preservation and not the
production of the product, and/or because the body concerned is in
gaseous form and not solid or liquid (including paste form), and/or
because the device does not act directly on the product concerned
but on its environment.
[0020] In the particular case of the production of a
biopharmaceutical product in liquid or paste form--and not in solid
form, using a pouch unit as indicated above, involving or
implementing an incident body as defined above, namely in solid
form and small in size and in particular fractionated--or liquid
form (including paste form) and not in gaseous form, there is
consequently the need to act directly on the biopharmaceutical
product--and not on its environment alone, in such a way that at
one or more times or stages, the incident body is necessarily
within the biopharmaceutical product itself and at one or other
times or stages, it is not or should not be within the
biopharmaceutical product itself.
[0021] The purpose of the invention is therefore to meet this
requirement.
[0022] For this purpose, according to a first aspect, the invention
has as its object a process for the production of a
biopharmaceutical product in substantially liquid or paste form by
a physical-chemical-biological production process, in which: [0023]
A pouch unit is provided that includes a pouch that defines an
inside space that can contain the biopharmaceutical product during
its production process, and said pouch unit is limited by a
continuous wall that is flexible, airtight, and non-degradable, and
that can be in direct contact by its inside face with the
biopharmaceutical product and can contain it, and, combined with
the pouch, at least one port, and, if necessary, at least one
functional device, [0024] The biopharmaceutical product that is not
totally finished or components of the latter is/are provided, and
the pouch is filled with said product or components, thus
constituting the contents of the pouch, [0025] The process for
production is implemented in and with the pouch unit, and during
this process, at least one incident body that is solid and small in
size or liquid that is within the biopharmaceutical product is used
or generated at at least one time or stage of the production
process.
[0026] This process is such that: [0027] A pouch unit that is
selected for incorporating an inherent means of support and
replacement is provided: [0028] Formed by or integrated in the wall
of the pouch or in at least one port or functional device, in such
a way as to be able to be accessible from the inside space of the
pouch and in direct physical contact with the contents of the
pouch, [0029] Arranged in such a way as to be functionally able to
be loaded with the incident body and to make possible the passage
of the incident body between one and the other of the inherent
means of support and replacement and within the contents of the
pouch, [0030] Being functionally active per se or as a consequence
of a dedicated activation operation, [0031] And the pouch unit is
used in such a way that the inherent means of support and
replacement is in direct physical contact with the contents of the
pouch and in such a way that with the inherent means of support and
replacement being functionally active, the incident body passes
substantially between one and the other of the inherent means of
support and replacement and within the contents of the pouch in
such a way that the incident body is substantially loaded on the
inherent means of support and replacement when it is not or should
not be substantially within the biopharmaceutical product.
[0032] According to the embodiments, the solid incident body is
individual or is broken into a number, more specially a large
number, of units or pieces.
[0033] According to the embodiments, the solid incident body is of
a dimension on the order of, or less than, or significantly less
than, a millimeter, down to molecular size.
[0034] According to the embodiments, the pouch unit is used in such
a way that the incident body is moved, in a substantial way,
between the biopharmaceutical product and the inherent means of
support and replacement, in the direction that goes from the first
to the second or in the direction that goes from the second to the
first.
[0035] According to one embodiment and different possible variants,
the inherent means of support and replacement is functionally
active in response to the value taken on by at least one
physical-biological-chemical condition of the contents of the pouch
or in response to the value taken on by the variation of such a
physical-biological-chemical condition or in response to a
dedicated activation operation of a physical, biological, or
chemical nature.
[0036] According to the embodiments, before filling with contents,
the inherent means of support and replacement is not loaded with
the incident body or, in contrast, is substantially loaded with the
incident body.
[0037] According to the embodiments, once the biopharmaceutical
product has been produced and is in the pouch, the inherent means
of support and replacement is not loaded with an incident body, or,
in contrast, is substantially loaded with the incident body.
[0038] According to a second aspect, the invention has as its
object a pouch unit that is specially designed for the
implementation of the process for the production of a
biopharmaceutical product in the substantially liquid or paste form
that was just described, including a pouch that defines an inside
space that can contain the biopharmaceutical product during its
production process, limited by a continuous wall that is flexible,
airtight, and non-degradable, and that can be in direct contact by
its inside surface with the biopharmaceutical product, and can
contain it, and, combined with the pouch, at least one port, if
necessary at least one functional device.
[0039] The pouch unit incorporates an inherent means of support and
replacement: [0040] Formed by or integrated in the wall of the
pouch or in at least one port or functional device, in such a way
as to be able to be accessible from the inside space of the pouch
and in direct physical contact with the contents of the pouch,
[0041] Arranged in such a way as to be functionally able to be
loaded with the incident body and to make possible the passage of
the incident body between one and the other of the inherent means
of support and replacement and within the contents of the pouch
itself, [0042] Functionally active per se or as a consequence of a
dedicated activation operation.
[0043] The pouch unit is implemented such that the inherent means
of support and replacement is in direct physical contact with the
contents of the pouch and such that, with the inherent means of
support and replacement being functionally active, the incident
body passes substantially between one and the other of the inherent
means of support and replacement and within the contents of the
pouch itself and is substantially loaded on the inherent means of
support and replacement when it is not or should not be
substantially within the biopharmaceutical product.
[0044] According to the embodiments, the inherent means of support
and replacement consists of or comprises a membrane or a coating or
a surface treatment of the wall of the pouch or at least one port
or functional device, or a body of support and replacement, or a
compartment of support and replacement.
[0045] According to one embodiment, the inherent means of support
and replacement is located toward the inside surface of the wall of
the pouch or at least one port or functional device that forms it
or integrates it.
[0046] According to the embodiments, the inherent means of support
and replacement is located on the entire surface or only a portion
of the surface of a face of the pouch or at least one port or
functional device that forms it or integrates it by then being
either located on or distributed over this surface.
[0047] With the pouch unit having, during the process for the
production of the biopharmaceutical product, a lower part, an upper
part, and a median part, according to the embodiments, the inherent
means of support and replacement is located at least in the lower
part or at least in the lower part and in the median part of the
unit.
[0048] According to the embodiments, an inherent means of support
and replacement has a surface area for replacement with the
contents of the pouch during the process for the production of the
biopharmaceutical product that is larger than, more specially
significantly larger than, more specially on the order of a
multiple of, the surface area of the inside face of the wall of the
pouch or at least one port or functional device that forms it or
integrates it, and that is in direct contact with the contents of
the pouch, in particular as a result of the composition of the
inherent means of support and replacement, or the wall of the pouch
or at least one port or functional device that forms it or in which
it is integrated or the configuration of the inherent means of
support and replacement on the wall of the pouch or at least one
port or functional device that forms it or in which it is
integrated.
[0049] According to the embodiments, the pouch is a 2D pouch or a
3D pouch.
[0050] According to a third aspect, the invention also has as its
object a pouch unit before filling with contents in which,
according to the embodiments, the inherent means of support and
replacement is not loaded with the incident body or, in contrast,
is substantially loaded with the incident body.
[0051] According to a fourth aspect, the invention also has as its
object a pouch unit that is filled with finished biopharmaceutical
product, in which, according to the embodiments, the inherent means
of support and replacement is not loaded with the incident body or,
in contrast, is substantially loaded with the incident body.
[0052] According to a fifth aspect, the invention also has as its
object a unit that comprises, in the first place, a pouch unit as
it was described in which the inherent means of support and
replacement is functionally active as a consequence of a dedicated
activation operation, and, in the second place, means for
activation of the inherent means of support and replacement of a
physical, biological or chemical nature.
[0053] According to one embodiment, the activation means consist of
the biopharmaceutical product that is in the inside space of the
pouch unit and that has properties that can activate the inherent
means of support and replacement.
[0054] According to one embodiment, the activation means are
located outside of the pouch unit.
[0055] Several embodiments of the invention will now be described
using drawings, in which:
[0056] FIG. 1 is a diagrammatic perspective view of a 3D pouch with
gussets that is part of a pouch unit that is specially designed for
implementing a process for the production of a biopharmaceutical
product in a substantially liquid or paste form according to the
invention, with the pouch unit incorporating an inherent means of
support and replacement, whereas during the process for the
production of biopharmaceutical product, at least one incident body
is used or generated and whereas the pouch unit is implemented in
such a way that the inherent means of support and replacement is in
direct physical contact with the contents of the pouch and in such
a way that with the inherent means of support and replacement being
functionally active, the incident body passes substantially between
one and the other of the inherent means of support and replacement
and within the contents of the pouch in such a way that the
incident body is substantially loaded on the inherent means of
support and replacement when it is not or should not be
substantially within the biopharmaceutical product.
[0057] FIG. 2 illustrates, on the one hand, the relative
arrangement of the inherent means of support and replacement
relative to the pouch unit and to the contents of the pouch, and,
on the other hand, the two functions of the inherent means of
support and replacement.
[0058] FIGS. 3 to 13 are eleven views, in transverse cutaways, on a
larger scale illustrating different possible embodiments of the
inherent means of support and replacement that the pouch unit
incorporates.
[0059] The description refers to the definitions provided above
that involve the biopharmaceutical product P, its substantially
liquid or paste form, the process for the production of such a
biopharmaceutical product P, a 2D pouch or a 3D pouch, the incident
body C, and, for this product, the qualification of solid and small
size, etc.
[0060] A pouch unit 1 as shown in FIG. 1 is part of a device that
is designed for the production of a biopharmaceutical product P,
i.e., a product that is obtained from biotechnology--culture media,
cellular cultures, buffer solutions, artificial nutrition liquids,
blood products and derivatives of blood products--or a
pharmaceutical product or more generally a product that is designed
to be used in the medical field. Such a biopharmaceutical product P
has the characteristic of being in a substantially liquid or paste
form, being totally or at least in a very predominant and
quantitatively prominent way, in liquid or paste form, even when,
if necessary, it comprises within itself a solid body in a very
small quantity.
[0061] The production of the biopharmaceutical product P consists
of one or more phases of a physical-chemical-biological process
during which the biopharmaceutical product P is completely or
partly manufactured before reaching the finished state that makes
possible its direct use or a semi-finished stage that makes
possible a subsequent use, such as, for example, an addition of one
or more components, a mixture, an aeration, a filtration, a
reaction, a heating or a cooling . . . .
[0062] According to one characteristic of the production process,
during the course of the latter, one or more incident body(ies) C
is/are used or generated (which includes the case where it is used
and generated). Such an incident body C is solid and small in size
or is liquid (including paste form) and, at at least one time or
stage of the production process, it is necessarily substantially
within the biopharmaceutical product P while at at least one other
time or stage of the production process, it is not or should not be
within the biopharmaceutical product P, in that in a very
predominant and quantitatively prominent way, the incident body C,
respectively, is located and is not located within the
biopharmaceutical product P. Such an incident body C has a small to
very small and even minute weight and volume relative to the weight
and volume of the biopharmaceutical product P.
[0063] Such an incident body C is solid and small in size, having a
certain cohesion or a certain consistency, or is liquid (including
paste form), in any case not being gaseous, and having, if it is
solid, a dimension on the order of, or less than, or significantly
less than, a millimeter, down to molecular size, where this is
understood for each unit or piece.
[0064] As appropriate, such an incident body C, if it is solid, is
individual or broken into a number, more specially a large number,
of units or pieces.
[0065] Such an incident body C is varied, concerning its substance,
its nature, its structure, its composition, its function, its
origin, its properties, its usefulness or its harmfulness . . . .
It may involve, for example, a body that falls within the final
composition of the biopharmaceutical product P or falls within its
initial composition or active ingredients or wastes or reaction
by-products or impurities or a catalyst, activator, regulator or a
toxin or an antibiotic or a body that acts on one or more
physical-biological-chemical conditions of the biopharmaceutical
product P or one or more physical-biological-chemical conditions
that prevail(s) in the pouch or antibody, cells, or bacteria.
[0066] The pouch unit 1 includes a pouch 2 that, according to the
embodiments, is a so-called 3D pouch with gussets as shown in FIG.
1, or a so-called 2D pouch, not shown.
[0067] The pouch 2 defines an inside space 2a, able to contain the
contents of the pouch during the production of the
biopharmaceutical product P, in particular the biopharmaceutical
product P itself, during its production.
[0068] The pouch 2 is limited by a wall 3, continuous as a whole,
made of a plastic film. It is flexible, airtight and
non-degradable. The film that forms the wall 3 is single-material
or not, single-layer or not. The--or each of the--constituent
material(s) of the film is/are selected from among the materials
that satisfy the above-mentioned requirements, as well as the
mechanical strength requirements.
[0069] The wall 3 has an outside face 3a and an inside face 3b.
"Outside" is defined as what is not located in the pouch 2, and
"inside" is defined as what is located in the pouch 2 and limits
the inside space 2a.
[0070] The pouch 2 can be in direct contact by its inside face 3b
with the contents of the pouch 2, in particular the
biopharmaceutical product P, and can contain it.
[0071] The pouch 2 is arranged to support at least one port 4, for
example a port for filling and a port for emptying. "Port" is
defined as any means of communication between the outside and the
inside of the pouch 2, which is open at one or more times or in one
or more stages when the communication is desired, or, if not, is
sealed.
[0072] At least one functional device 5, such as a device for
mixing, aeration, filtration, measuring (whereby this list is not
exhaustive), and comprising a suitable element, such as a mixing
propeller, aerator, filter, probe (whereby this list is not
exhaustive), is combined in general, and if necessary, with the
pouch 2. Such an element is at least partly placed in the inside
space 2a of the pouch 2.
[0073] The at least one port 4 or functional device 5 has, in line
with the wall 3 of the pouch 2, an inside face that is located in
the pouch 2.
[0074] The pouch unit 1, at least during the process for the
production of the biopharmaceutical product P, is arranged to have
a lower part 2b, an upper part 2c, and a median part 2d.
[0075] In a typical embodiment, the pouch 2 comprises one or a
number of ports 4 for filling in the upper part 2c (such as the
port 4 shown in FIG. 12) and a port 4 for emptying into the lower
part 2b, and a functional device 5 for mixing in the lower part 2b
(FIG. 13). Such an embodiment does not exclude others.
[0076] The device that is designed for the production of the
biopharmaceutical product P can comprise, if necessary, an outside
rigid container for receiving the pouch unit 1 in its inherent
inside space.
[0077] The pouch unit 1 incorporates an inherent means of support
and replacement 6. "Incorporating" means that the means 6 forms a
cohesive, in particular an inseparable, unit with the pouch unit 1.
"Inherent" means that the functions of support and replacement that
describe the means 6 belong to the latter and characterize it.
[0078] The inherent means of support and replacement 6 is formed by
or integrated in the wall 3 of the pouch 2 or in at least one port
4 or functional device 5. In so doing, the inherent means of
support and replacement 6 is able to be accessible from the inside
space 2a of the pouch 2 and in direct physical contact with the
contents of the pouch 2, in particular the biopharmaceutical
product P.
[0079] The inherent means of support and replacement 6 is arranged
in such a way as to be functionally capable of being able to be
loaded with an incident body C and to make possible the passage of
this incident body C between one and the other of the inherent
means of support and replacement 6 and within the contents of the
pouch 2. The means 6 is therefore able to ensure a first function
that consists in being able to be loaded with the incident body C
and also a second function that consists in making possible the
passage of the incident body C between one and the other of the
inherent means of support and replacement 6 and within the contents
of the pouch 2, in particular the biopharmaceutical product P.
[0080] "Loaded" means that the incident body C is carried or
captured by or held or located on or assimilated or adsorbed or
absorbed by the inherent means of support and replacement 6 in such
a way that under normal conditions and without other intervention,
it cannot disseminate or be disseminated, at least substantially,
outside of the inherent means of support and replacement 6 or its
immediate proximity.
[0081] "Passage" means that the incident body C migrates and is
moved from the inherent means of support and replacement 6 or its
immediate proximity to the biopharmaceutical product P or to one or
more of the components of the latter, in the direction that goes
from the first to the second (arrows F1, FIG. 2) or from the second
to the first (arrows F2, FIG. 2). In the case where there are two
(or more) incident bodies C1 and C2, they can "pass" in the two
directions (arrows F3 and F4, FIG. 2).
[0082] The inherent means of support and replacement 6 is
functionally active per se, in particular permanently or as a
consequence of a dedicated activation operation, in particular from
a given time.
[0083] The process for the production of the biopharmaceutical
product P is such that a pouch unit 1 is used as it was described
above, and the biopharmaceutical product P, not totally finished,
or components of the latter, and the pouch 2, then in particular
empty, is filled by thus constituting the contents of the pouch
2.
[0084] The production process is implemented in and with the pouch
unit 1, and during this process, the incident body C is used or
generated, or the latter is used or generated. For example, with
the latter's sole object being to illustrate the invention, the
production process can consist in adding a component, for example,
in finely-divided solid form--from the outside of the pouch 2 and
via a port 4--to the contents in liquid or paste form that are
already in the pouch 2 for having been placed there previously and
in mixing the whole by means of a functional device 5, here a
mixer. With the process generating, for example, wastes
constituting here the incident body C, it is necessary to remove
them from within the biopharmaceutical product P during production.
This is the dual function performed by the inherent means of
support and replacement 6 that will capture the wastes/incident
body C in such a way that the finally finished biopharmaceutical
product P is free thereof.
[0085] As appropriate, the pouch unit 1 is totally filled, or it is
only partially filled, in its lower part 2b or at least in the
lower part 2b and in all or part of the median part 2d.
[0086] As is expressly evident from FIG. 2, which illustrates, on
the one hand, the relative arrangement of the inherent means of
support and replacement 6 relative to the pouch unit 1 and to the
contents of the pouch 2, and, on the other hand, the two functions
of the inherent means of support and replacement 6, the pouch unit
1 is used in such a way that the inherent means of support and
replacement 6 that is submerged at least partially by the contents
of the pouch 2 are in direct physical contact with these contents,
in particular the biopharmaceutical product P, and in such a way
that with the inherent means of support and replacement 6 then
being functionally active, the incident body C passes directly
substantially between one and the other of the inherent means of
support and replacement 6 and within the contents of the pouch 2,
in particular the biopharmaceutical product P.
[0087] Thus, the incident body C is substantially loaded on the
inherent means of support and replacement 6 when it is not or
should not be substantially within the biopharmaceutical product P,
whereas at at least a time or stage of the production process, it
is necessarily substantially within the biopharmaceutical product
P.
[0088] For example, the incident body C is a waste that is produced
within the biopharmaceutical product P during the production
process, and this waste is then captured by the inherent means of
support and replacement 6 by being isolated and separated from the
biopharmaceutical product P. Or, conversely, the incident body C is
an activator of the process of the production of the
biopharmaceutical product that is not present within the latter at
the beginning of the process, but is found there subsequently,
released by the inherent means of support and replacement 6 on
which it is originally loaded.
[0089] According to the embodiments, the inherent means of support
and replacement 6 consists of, or comprises, a membrane (FIGS. 3,
5, 6, 7, 8) or a coating (FIG. 4) or a surface treatment (FIG. 9)
of the wall 3 of the pouch 2 (FIGS. 3 to 11) or at least one port 4
(FIG. 12) or functional device 5 (FIG. 13), or a support and
replacement body (FIGS. 10), or a support and replacement
compartment (FIG. 11).
[0090] According to one embodiment, the inherent means of support
and replacement 6 is located toward the lower face 3b of the wall 3
of the pouch 2 (FIGS. 2 to 5 and 7 to 11) or at least one port 4
(FIG. 12) or functional device 5 (FIG. 13) that forms it or
integrates it. This embodiment does not exclude others, whereby the
inherent means of support and replacement 6 can be located toward
the outside face 3a of the wall 3 of the pouch 2 whereas it is able
to be accessible from the inside space 2a of the pouch 2 and in
direct physical contact with the contents of the pouch 2 (FIG.
6).
[0091] According to one embodiment, the inherent means of support
and replacement 6 is located on the entire surface of the face of
the wall 3 of the pouch 2 (FIGS. 3 to 6, 8 and 9) or at least one
port 4 (FIG. 12) or functional device 5 (FIG. 13), which forms it
or integrates it. According to another embodiment, the inherent
means of support and replacement 6 is located on one portion of the
surface of the face of the wall 3 of the pouch 2 or at least one
port 4 or functional device 5 that forms it or integrates it by
then being either located (FIG. 7) or distributed over this
surface.
[0092] According to one embodiment, the inherent means of support
and replacement 6 is located in the lower part 2b of the pouch unit
1 or in this lower part 2b and in all or part of the median part
2d.
[0093] According to one embodiment, quite specially in the case
where the pouch unit 1 is only partially filled, the inherent means
of support and replacement 6 is located in the lower part 2b of the
pouch unit 1 or in this lower part 2b and all or part of the median
part 2d. According to another embodiment in the case where the
pouch unit 1 is totally filled, the inherent means of support and
replacement 6 can be located in the upper part 2c of the pouch
unit, as is the case if it is located on a port 4 such as the port
4 that is shown in FIG. 12.
[0094] According to possible embodiments, the inherent means of
support and replacement 6 has a surface area for replacement with
the contents of the pouch 2 during the process for the production
of the biopharmaceutical product P that is larger than, more
specially significantly larger than, more specially on the order of
a multiple of, the surface area of the inside face 3b of the wall 3
of the pouch 2 or at least one port 4 or functional device 5 that
forms it or integrates it, and that is in direct contact with the
contents of the pouch 2.
[0095] Such a larger surface area for replacement is obtained as a
result of the composition of the inherent means of support and
replacement 6, or the wall 3 of the pouch 2 or at least one port 4
or functional device 5 that forms it or in which it is integrated
or the configuration of the inherent means of support and
replacement 6 on the wall 3 of the pouch 2 or at least one port 4
or functional device 5 that forms it or in which it is integrated
(FIGS. 8 and 9).
[0096] According to a functional embodiment, which can be combined
with structural embodiments, the inherent means of support and
replacement 6 is active per se, for example, because its nature
makes it possible to capture or release the incident body C at any
time and permanently, without requiring an action to be taken to do
so.
[0097] According to another functional embodiment, the inherent
means of support and replacement 6 is not active per se at any time
and permanently but it requires being made active as a consequence
of a dedicated activation operation.
[0098] Such a dedicated activation operation of the inherent means
of support and replacement 6 and the means for its implementation
may be the object of different embodiments.
[0099] According to one embodiment, the inherent means of support
and replacement 6 is made active in response to the value taken on
by at least one physical-biological-chemical condition of the
biopharmaceutical product P or at least one
physical-biological-chemical condition existing in the pouch 2.
Such a physical-biological-chemical condition is, for example, the
temperature, the pH, the composition, the contents of a certain
body, the presence of a certain microorganism . . . .
[0100] According to another embodiment, the inherent means of
support and replacement 6 is made active in response to the value
not of the physical-biological-chemical condition as such, but in
response to the variation of such a physical-biological-chemical
condition.
[0101] According to another embodiment, the inherent means of
support and replacement 6 is made active in response to a dedicated
activation operation of a physical, biological or chemical nature,
such as heat, stirring . . . .
[0102] Thus, in these embodiments, means for activating the
inherent means of support and replacement 6 of a physical,
biological or chemical nature are provided that are structurally
separate from the pouch unit 1 but are designed to be combined
functionally with it during the activation of the inherent means of
support and replacement 6. If necessary, these activation means
consist of the biopharmaceutical product P that has properties of a
physical, biological or chemical nature and that can activate the
inherent means of support and replacement. According to the
embodiments, these activation means are located outside of the
pouch unit 1 or in the inside space 2a when, for example, they
consist of the biopharmaceutical product P.
[0103] In the case of FIG. 3, the inherent means of support and
replacement 6 is formed by a layer 7 that totally and continuously
coats the inside face 3b of the film of the wall 3 or the wall 3
itself. In such an embodiment, the inherent means of support and
replacement 6 has a surface area for replacement with the
biopharmaceutical product P during its production and/or its
preservation that is substantially equal to the surface area of the
inside face 3b of the pouch 2 of the pouch unit 1.
[0104] In the case of FIG. 4, the inherent means of support and
replacement 6 is formed by a continuous coating 8 over the entire
inside face 3b of the film of the wall 3 or the wall 3 itself.
[0105] In the case of FIG. 5, the inherent means of support and
replacement 6 is formed by a continuous layer 9 that is sandwiched
between the outside face 3a and the inside face 3b of the film of
the wall 3 or the wall 3 itself, over the entire surface of the
film, or the wall.
[0106] In the case of FIG. 6, the inherent means of support and
replacement 6 is formed by a layer 10 that totally and continuously
coats the outside face 3a of the film of the wall 3 or the wall 3
itself, with the film of the wall 3 or the wall 3 itself then being
able to allow the replacement of the incident body C, in its entire
thickness, from the inside space 2a of the pouch 2 to the outside,
and vice versa.
[0107] In the case of FIG. 7, the inherent means of support and
replacement 6 is formed by a layer 11 that forms a type of part (or
"patch") 11 that locally coats the inside face 3b of the film of
the wall 3 or the wall 3 itself. In this case, either a single such
part 11 of suitable surface and shape, located at the desired spot
of the film of the wall 3 or the wall 3 itself, or several parts
11, arranged and distributed according to a suitable distribution,
can be provided.
[0108] In the case of FIG. 8, the inherent means of support and
replacement 6 is or comprises a membrane 12 that is more or less an
integral part of the film of the wall 3 or the wall 3 itself, on
the inside face 3b. For example, the membrane can be folded in a
more or less significant way on itself.
[0109] In the case of FIG. 9, the inherent means of support and
replacement 6 is formed by crevices 13 or an irregular surface
condition with recesses or cavities of the film of the wall 3,
obtained by particle bombardment, chemical attack, . . . . In such
an embodiment, the inherent means of support and replacement 6 has,
by the very fact of the configuration that is provided thereto, a
surface area for replacement with the biopharmaceutical product P
during its production that is larger than the surface area of the
inside face 3b of the pouch 2. For example, the inherent means of
support and replacement 6 can have a surface area for replacement
on the order of several times, and even a large number of times,
the surface area of the inside face 3b of the pouch 2.
[0110] In the case of FIG. 10, the inherent means of support and
replacement 6 is a solid body 14, for example carried by the film
of the wall 3 or by the wall 3 itself, over or toward the inside
face 3b. In such an embodiment, the inherent means of support and
replacement 6 has, in itself, a surface area for replacement with
the biopharmaceutical product P during its production that is
larger than the surface area of the inside face 3b of the pouch 2.
For example, the means 6 can have a surface area for replacement on
the order of several times, and even a large number of times, the
surface area of the inside face 3b of the pouch 2.
[0111] In the case of FIG. 11, the inherent means of support and
replacement 6 consists of a compartment 15 that is limited by a
wall 16 that makes possible the replacement between the inside and
the outside of the compartment 16. As above, the inherent means of
support and replacement 6 occupies the entire surface or only a
portion of the surface of the film of the wall 3 or by the wall 3
itself by being either located or distributed relative to this
surface.
[0112] In the case of FIG. 12, the inherent means of support and
replacement 6 is formed by or integrated in a port 4, while being,
as above, able to be accessible from the inside space 2a of the
pouch 2 and in direct physical contact with the contents of the
pouch 2. This embodiment includes the case where the inherent means
of support and replacement 6 is formed by or integrated not
directly in the port 4 itself, but indirectly, namely in an element
for supporting the port 4.
[0113] In the case of FIG. 13, the inherent means of support and
replacement 6 is formed by or integrated in a functional device 5,
while being, as above, able to be accessible from the inside space
2a of the pouch 2 and in direct physical contact with the contents
of the pouch 2. This embodiment includes the case where the
inherent means of support and replacement 6 is formed by or
integrated not directly in the functional device 5 itself, but
indirectly, namely in an element for supporting the functional
device 5.
[0114] Of course, different structural embodiments of those
described above can be combined with one another, either for the
same incident body C or for different incident bodies C.
[0115] The process for production and the pouch unit 1 can be the
object of several different embodiments relative to the time when
the inherent means of support and replacement 6 is loaded with the
incident body C and the time when it is not loaded with the
incident body C, relative to the time before the filling of the
pouch 2 and once the biopharmaceutical product P is produced.
[0116] In one embodiment, before filling with contents, the
inherent means of support and replacement 6 is not loaded with the
incident body C.
[0117] In another embodiment, before filling with contents, the
inherent means of support and replacement 6 is substantially loaded
with the incident body C.
[0118] In one embodiment, after the biopharmaceutical product P has
been produced, the inherent means of support and replacement 6 is
not loaded with the incident body C.
[0119] In another embodiment, after the biopharmaceutical product P
has been produced, the inherent means of support and replacement 6
is substantially loaded with the incident body C.
[0120] These embodiments are combined with one another for the same
inherent means of support and replacement 6 and the same incident
body C.
[0121] Thus, before filling the pouch 2, the inherent means of
support and replacement 6 is not loaded with the incident body C,
and after the biopharmaceutical product P has been produced, in
contrast, it is loaded with the incident body C. This embodiment is
applied, for example, with an incident body C that is an
undesirable body that does not exist at the beginning of the
process for the production of the biopharmaceutical product P, but
is produced during this production process and that is desired to
be eliminated within the biopharmaceutical product P itself.
[0122] In another embodiment, before filling the pouch 2, the
inherent means of support and replacement 6 is substantially loaded
with the incident body C, and after the biopharmaceutical product P
has been produced, in contrast, it is not loaded with the incident
body C. This embodiment that is applied, for example, with a body C
can then be an incident body that is necessary to the process for
the production of the biopharmaceutical product P, existing at the
beginning of the production process, consumed during this process,
and not existing at the end.
* * * * *