EP3481737A1 - 3-d flexible bag to be filled for biopharmaceutical fluids and method for creating such a bag - Google Patents

Abstract

The 3-D flexible bag (1) to be filled with a biopharmaceutical product is the result of the assembling of two wall elements (2, 3) and of two gussets (11, 12). At least one connection port (4, 6) is also provided, for filling and/or emptying. A substantially parallelepipedal configuration is obtained in a filled state thanks to the unfolding of the gussets combined with the folding of flaps (21, 22, 31, 32) of the two wall elements. A transverse weld (140, 150), formed at one end, connects the two wall elements (2, 3) of the bag and extends continuously, keeping in a folded-flat state: – an elongate edge portion of one gusset (11); – an elongate edge portion of the other gusset (12). This transverse weld has a length corresponding to a determined dimension (L2) of the flexible bag in the parallelepipedal configuration.

Description

 3D flexible pouch to be filled for biopharmaceutical fluids, and method for making such a pouch

 The invention relates to the field of conditioning of biopharmaceutical fluids and more particularly relates to a flexible reservoir to be filled, in the form of a flexible bag 3D (three dimensions), which must generally be placed in a rigid container. The invention also relates to an equipment and a method for producing such a 3D flexible pouch.

 "Biopharmaceutical product" means a product derived from biotechnology, culture media, cell cultures, buffer solutions, artificial nutrition liquids, blood products and blood product derivatives, or a pharmaceutical product or more generally a product for use in the medical field. Such a product is in liquid form, pasty, or possibly powdery. The invention also applies to filling flexible bags with other products but subject to similar requirements with regard to their packaging.

In 3D bags of this type, for single use and intended to receive a biopharmaceutical product (international class A61J 1/05 according to the international or cooperative classification), the volume is typically delimited by a lower end wall, a wall upper end and a flexible sidewall, which can be in two extreme states - folded flat and unfolded unfolded. The 3D pocket may be deformed to move from one state to another or to any intermediate state. The walls of the pocket, composed of a monolayer or multilayer film, of plastic material such as polyethylene or a complex comprising polyethylene, delimit an internal space which, in the folded state, is of minimum volume and, at the Unfolded and deployed state is maximum. This space is intended to receive the biopharmaceutical product for storage, processing, transport. Such a flexible pouch, biocompatible, disposable, can be large volume of 2 or 5 liters at least, up to 3000 liters, or even more, which justifies that it is called 3D. Such a pocket thus offers a large capacity while being easily stored. An example of such a pocket is described in the international application WO00 / 04131 or in the document FR 2781202. In contrast to the pockets of which only the bottom has a bellows (with an increased risk of breakage), it is preferable to create two opposite bellows as illustrated in Figures 3 to 5 of WO00 / 04131. The welds at the top and the bottom of the pocket are made in K, before proceeding to a cutting portions of angles (cut to remove the outer parts of the films beyond the weld areas).

 Sometimes the products in this type of pocket are used thousands of miles from where the bag was filled. These products are often of high financial value, and often of high value to the health of individuals since they can be used for example in the manufacture of drugs intended for human health. It is therefore essential that these bags surely reach their destination, full of the liquid with which they were originally filled and not contaminated.

 In some options, the pocket may also include sensors

(temperature, pH, physico-chemical characterization of the biomass) and / or a treatment member, for example in the form of a mixer operable by mechanical coupling or movable by magnetic drive.

 Given the many constraints that these bags are subjected to, especially during their transport or during certain treatments of the biopharmaceutical product: acceleration, braking, sloshing, shaking, vibration, etc. (ie many forces including shear forces that tend to alter the film that constitutes them, especially in sensitive places such as creases), it is essential to form the connection port or ports, used in particular for filling or emptying, in a portion of the pocket that is separated from the weld areas. In addition, these connection ports are the only access to the internal space, the pockets being devoid of hinged or removable cover, flap opening / closing, peelable or tearable portion, and devoid of fragile areas. The pockets do not have areas of weakness in the weld areas.

It can be provided that the bag is provided with a port for entering or introducing a biopharmaceutical product and a gas supply port, for example on the side of an upper end wall. Corresponding supply lines, each connected to a power source (which is generally external to the rigid container for carrying and storing the filled 3D pocket), are connected to these respective ports. Alternatively, filling can be achieved using a lower feed line. The document EP-B1-0326730 describes a filling of this type, with the disadvantage that the flexible bag is more complex, it being provided with side flaps, which limits the interest of this type of option. It is generally desirable to limit the complexity and cost of the flexible pouch 3D which is a disposable consumable (this is the flexible pouch without the potential accessories).

 The K-weld is also applicable to medical or medicinal bags (single use also) which have a large upper opening in a parallelepipedal expanded configuration, as described in particular in US Pat. No. 6,332,711 B1. In this case, it is preferable to provide a lower connection port for emptying.

 In practice, it is desirable that the flexible pouch be able to deploy without undesirable crease which limits the effective filling volume. Indeed, filling usually requires human supervision, due to the fact of deployment defects including the flexibility of the pocket and the mobility of the supply lines. The loading system described in WO 2015/118269 allows guidance to avoid the appearance of undesirable fold but this requires a very specific implementation.

 There is therefore a need for a robust 3D pocket adapted to the preservation, treatment, and / or transport of biopharmaceutical fluid (volume of 50 liters and more), which remains simple enough to produce and limits the risk of unwanted bending. in the filling phases.

 According to a first aspect, the invention relates to a flexible pouch 3D (bellows) for biopharmaceutical product, provided with at least one connection port for filling and / or emptying, and designed to deploy from a planar empty configuration to a substantially parallelepipedic configuration in a filled state.

 The flexible 3D pocket presents:

 a first wall element consisting of a film and making it possible to define a front face,

 a second wall element consisting of a film and making it possible to define a rear face,

 a first bellows and a second bellows, each connected to two lateral edges of one and the other of the first and second wall elements, the first bellows and the second bellows consisting of respective films cut in one piece and each capable of folding, typically in two, along an inwardly fold line extending between two opposite ends of the flexible pouch, and

the at least one connection port, formed exclusively in one of the first wall element and the second wall element, the first wall element and the second wall element being welded to each other in a transverse direction, at least one of the two opposite ends.

 In this pocket, the first wall element and the second wall element have in said transverse direction a determined dimension (typically the width) which is, at least in the planar configuration, substantially the same:

 - in the front and rear faces,

 and at least one of the two opposite ends, where a continuous weld extends over the whole of the determined dimension,

 knowing that the continuous weld further allows, in the same end of the pocket, to maintain in a flat folded state an edge portion (elongate portion) of the first bellows and an edge portion (elongate portion) of the second bellows, both in the planar configuration and in the parallelepipedic configuration. The folded flat state typically corresponds to a non-modifiable configuration in which each edge portion covered by the wall elements is kept folded in half.

 Thanks to these provisions, the pocket has a welded end sufficiently long and rigid for both:

 guiding a correct unfolding of the first and second bellows, as well as a correct folding of the first and second wall elements to reduce the initial distance between the two opposite ends;

 - reduce the risk of rupture at the connecting end where all the films constituting the pocket meet.

On the side of this end, one can form a face which is thus more robust than when making a weld K. The design process can be further simplified by limiting to four junction angles between two rectilinear welds, welds being performed while the first and second wall members of the pocket are kept parallel to each other.

 According to a feature, in the planar configuration, the two fold lines are separated by a transverse spacing which is less than half, and preferably less than one quarter, of the determined dimension.

 According to one feature, in the planar configuration of the flexible bag 3D, the fold line of each bellows is rectilinear and the continuous weld is transverse (typically perpendicular) to each rectilinear fold line of the bellows.

According to one feature, the flexible pouch is provided with at least one connection port placed in a flap defined by the first wall element, the side of the continuous weld and with a spacing relative to this weld. Thus, it is allowed to introduce a biopharmaceutical liquid or to drain such a liquid on the side of an elongated welded edge. For emptying in particular, it is observed that the bellows retain their orientation, which facilitates the smooth running of the drain. Indeed, the type of junction between the bellows and the first and second wall elements, with such an elongated welded edge, significantly limit the risk of crease formation (in particular cross-fold with respect to the predefined fold line for each bellows) which shows residual volumes of biopharmaceutical product retention.

 For filling in a rigid container, this configuration can also help to limit deployment defects related to the flexibility of the pocket. Thus, it has been observed with pockets without such an elongated welded edge that the flexible bag, because of large folds, hangs against the inner faces of the axial wall of the rigid container, causing unfolding defect and risk of degradation flexible pouch for single use.

 In various embodiments of the flexible pouch, it may further be possible to resort to one or more of the following provisions:

 - Two first flaps are provided, one of which is part of the first wall element and the other is part of the second wall element, the two first flaps being contiguous and forming:

 an outer face of the flexible pouch in the parallelepipedic configuration;

a first protruding strip which extends parallel to the front face and to the rear face, provided with a substantially rectilinear free edge, the first protruding strip projecting from said external face of the flexible pouch, in the parallelepipedic configuration, the continuous weld stiffening the entire first protruding band.

 - two second flaps are provided, one of which is part of the first wall element and the other part of the second wall element, the two second flaps being joined together forming a second projecting strip located opposite the first protruding band and provided with a substantially straight free edge.

the second protruding strip projects from another external face of the flexible pouch, the other external face being defined by the second flaps in the parallelepipedal configuration, extending parallel to the front face and to the rear face.

at least one of the first protruding band and the second protruding band: has a central weld portion made directly between an inner face of the first wall element and an inner face of the second wall element; and

 is more rigidified on either side of the central weld portion, in portions longer than the central weld portion, and preferably at least twice as long.

 the first protruding band and the second protruding band have an identical length and each flap among the first two flaps and the second two flaps is delimited by a U-shaped welding zone defining two right angles in the plane configuration.

 each U-shaped welding zone is designed and arranged to prevent, whatever the proportion of filling of the flexible pouch:

 unfolding a first triangular portion belonging to the first bellows and adjacent to an edge portion of the first bellows folded in two;

 - Unfolding a second triangular portion belonging to the second bellows and adjacent to an edge portion of the second bellows folded in half.

the first triangular portion and the second triangular portion extend substantially in the same plane along a flap chosen from one of the first two flaps and the second two flaps.

 the first bellows is delimited by two first longitudinal edges which extend from one to the other of the two opposite ends of the flexible bag, while the second bellows is delimited by two second longitudinal edges which extend from the one to the other of the two opposite ends.

 - The first two longitudinal edges are continuously welded and each U-shaped in the parallelepiped configuration, by delimiting in a rectangular manner a first face of the flexible bag which is defined by the first bellows in the parallelepiped configuration.

 - The two second longitudinal edges are continuously welded and each conform to U in the parallelepiped configuration, defining in a rectangular manner a second face of the flexible bag which is defined by the second bellows in the parallelepiped configuration.

the determined dimension is identical in the front face, the rear face and each of the said flaps, so that the first two flaps and the second two flaps together form two opposite rectangular faces of the flexible pocket in the parallelepipedic configuration and partially cover the first and second bellows.

 the films respectively constituting the first wall element, the second wall element, the first bellows and the second bellows are welded together by defining in the plane configuration a total of six welds, of which:

 two continuous welds formed at the two opposite ends and which extend in the transverse direction; and

 - four lateral welds perpendicular to the transverse direction.

 - each of the six welds is continuous and of a width at least equal to 5 mm.

each of the films constituting respectively the first wall element, the second wall element, the first bellows and the second bellows present locally, along the welds, a thickness which is not less than the average thickness of the films; average thickness being between 150 and 450 μιτι for each of these films.

- the following relation is satisfied:

 0.05 <D2 / L2 <0.5

where L2 denotes the determined dimension; and

 D2 denotes a transverse spacing between the first bellows and the second bellows, measured in said transverse direction.

the respective films are each composed of at least three non-metallic plastic layers, and are preferably transparent or translucent.

 the respective films each have a thickness of between 150 micrometers and 450 micrometers and a tensile strength of between 60 and 220 Newton.

the first bellows and the second bellows each present:

 a heat-sealable inner layer made of a material chosen from polyethylene and ethylene-vinyl acetate copolymer; and

 - A weldable outer layer, a material selected from polyethylene, polyamide, ethylene-vinyl acetate copolymer, polyamide and poly (ethylene terephthalate).

 in the parallelepiped configuration:

 the maximum extension of each of the first and second bellows is at least 15 cm between the first wall element and the second wall element.

the flexible pouch makes it possible to delimit an interior space at least equal to 2 L, preferably at least equal to 5 L. According to a second aspect, there is provided a method for manufacturing a flexible 3D pouch according to the invention to be filled by a biopharmaceutical product, in which process is carried out in a longitudinal direction of scrolling and transversely cut:

 a first wall element provided with two lateral edges consisting of a film and making it possible to define a front face,

 a second wall element provided with two lateral edges, consisting of a film and making it possible to define a rear face,

 a first bellows and a second bellows, each consisting of a film cut from one piece and delimited by two longitudinal edges,

knowing that each of the first bellows and the second bellows is inserted, in a folded state in two around a longitudinal fold line, between the first wall member and the second wall member, the first bellows and the second bellows being arranged with a transverse spacing relative to each other.

 This process more particularly comprises the steps which essentially consist of:

 longitudinally weld the two longitudinal edges of the first bellows to the first wall element and to the second wall element, respectively to one of the lateral edges of the first wall element and the second wall element, whereby two first lateral welds are obtained ;

 longitudinally weld the two longitudinal edges of the second bellows to the first wall element and to the second wall element, respectively to the other of the lateral edges of the first wall element and the second wall element, whereby two second lateral welds are obtained;

transversely welding the first wall element and the second wall element to form a welded end flange, and preferably two opposite welded end flanges, sandwiching between the first wall element and the second wall element; , respectively two layers of the first folded bellows in two and two layers of the second bellows folded in two, so that the first bellows and the second bellows are also welded in an end flange, and preferably two opposite end flanges, perpendicularly to their longitudinal edges in a planar empty configuration of the flexible bag (the first and second wall members thus being kept parallel), each longitudinal fold line extending between two opposite ends of the flexible bag in the planar configuration, so that the first bellows and the second bellows allow the pocket is expanded from the planar vacuum configuration to a substantially parallelepipedal configuration in a filled state, each end flange being continuously welded and defining a determined external dimension of the pocket which is common to the back face and the front face in the parallelepipedic configuration;

 - Insert, exclusively in one of the first film and the second film, a connection port for connecting a flexible supply line.

 According to one feature, two parallel opposite end flanges are welded in order to define the same determined external dimension (L2) of the flexible pouch at these ends, the first wall element and the second wall element having a rectangular perimeter in the flat configuration.

 According to a preferred option, the first wall element, the second wall element, the first bellows and the second bellows are defined by rectangular sheets having the same multilayer structure.

 Other features and advantages of the invention will become apparent from the following description of several embodiments, given by way of non-limiting examples, with reference to the accompanying drawings in which:

 - Figures 1A and 1B are perspective views showing, in a first embodiment, a flexible bag 3D before filling with a biopharmaceutical fluid.

 FIG. 2 is a perspective view of the flexible 3D pocket of FIGS. 1A-1 B, in the deployed state and filled with a biopharmaceutical fluid.

 - Figure 3 shows a logic diagram of steps representing the steps of assembly and trimming of four constituent films of the flexible bag 3D.

- Figure 4 is a detail sectional view illustrating an example of a welding step between a bellows and the adjacent wall elements of the flexible bag 3D.

 - Figure 5 is a perspective view illustrating an embodiment of two continuous welds to obtain a flexible pouch according to the first embodiment.

FIG. 6 is a cross-sectional view showing the arrangement of the four films in a web-shaped weld,

 - Figure 7 is a side view showing the bottom of a flexible bag 3D in the filled state and received in a storage device.

- Figure 8A is a perspective view illustrating the conformation of a first bellows of the flexible bag 3D, in the parallelepipedal configuration of the flexible bag. - Figure 8B is a sectional view only the first bellows, when the flexible bag 3D is in the same configuration as in Figure 8A, with the fold line fully included in the section plane.

 FIG. 8C is a sectional view similar to that of FIG. 8B, showing the rectilinear extension of the fold line of the first bellows when the flexible pouch

3D is in the plane configuration.

 FIG. 9 is a perspective view of a flexible 3D pocket according to an embodiment variant, having a K-weld at one of its ends.

 - Figure 9 is a perspective view of a flexible bag 3D according to an alternative embodiment, with a K-weld at one end.

 FIG. 10 is a perspective view of a flexible 3D pocket with an arrangement of the connection ports in a central zone of a wall element, between two flaps of this wall element.

 - Figure 1 1 is a perspective view of a flexible bag 3D according to the prior art. FIG. 12 represents an example of composition of the constituent films of the flexible pouch according to the invention.

 Hereinafter a detailed discussion of several embodiments of the invention with examples and reference to the drawings.

 In the various figures, identical references indicate identical or similar elements.

As can be seen in FIGS. 1A and 1B, the flexible pouch 1 which unfolds in three dimensions may have a planar configuration, in which two opposite wall elements 2, 3 define two opposite external main faces of the flexible pouch 1. It can be seen that this flexible pouch 1 has connection ports for filling and / or emptying. Here, the connection port 4 may allow to connect, according to a non-limiting example, a flexible pipe 5 to perform a drain. In this case, and as illustrated in FIG. 2, when the flexible pouch 1 is in a parallelepipedal expanded configuration, this connection port 4 of the flexible pouch 1 of the 3D type extends in a first end face W1. According to one option, one or more connectors 6 forming connection ports are provided here on the second end face W2 opposite the connection port 4, to allow filling of the flexible bag 1 (with typically several openings). entrance or supply). In general, at least one flexible supply line is provided to fill the flexible pouch 3D via a connection port. Here, the flexible pipes T1, T2 associated with the connectors 6 are of a kind known per se. Wall lateral flexible W3 has predefined folds, in particular fold lines FL1 and FL2 formed in bellows January 1, 12 during the design of the flexible bag 1, which facilitates a correct unfolding as the level of filling, typically by a biopharmaceutical fluid, rises.

 Of course, the position of the connection port or ports 4, 6 may vary, preferably by making the openings on one (preferably only one) of the wall elements 2 and 3. These connection ports 4, 6 are placed remote from the connection areas between the two wall elements 2 and 3 and they do not interfere with the unfolding of the bellows 11 and 12 of the flexible pouch 1 type 3D. The ports 4, 6 may be sealed in a manner known per se (in the example of FIG. 10, the ports are sealingly connected to a length of tube or pipe T1, T2 itself closed off, sealed, by a clamp generally called "clamp" (C1, C2) by the skilled person, an aseptic connector, or may include valves or non-return valves or other similar sealing systems).

 FIG. 7 illustrates an example of application of the flexible pouch 1. Here, the bottom defined by the first end face W1 is attached to the base portion B of a storage device 10, which can be used, if necessary, to carry the flexible pouch 1 type 3D in the filled state. The hose 5 to perform a drain is then able to pass through an orifice 05 located in the base portion B of the storage device 10. This cooperation with an orifice 05 makes it possible to position the first end face W1 of the flexible bag well. 1. In addition, the disappearance of the welds forming a K on the sides eliminates the constraints related to the poor positioning of these welds with respect to the storage device 10 that can cause leakage. In practice, the flexible bag 1 can be placed in the interior volume of such a storage device 10 before a filling step in biopharmaceutical fluid. The internal volume of the device 10 is accessible through an upper transverse opening, and possibly accessible using side doors. Figures 1 and 3 of WO 2015/1 18269 illustrate this type of storage device.

The increase in volume of the flexible bag 1 can be done by minimizing the risk of formation of bad fold in the W1 face. The side wall W3 can also inflate without hindrance and without a bad fold to go from an extreme state (completely flat) to another extreme state (by defining a parallelepipedal volume), resting on the internal face of the storage device 10. This type of storage device 10 may be in the form of a rigid container, possibly with a possibility of stacking. This is, in the case of Figure 7, an application for large volumes that reach or exceed 15 or 20 liters. This is the reason why it is in practice necessary to ensure the external maintenance of the flexible pouch 1, once filled with content. Some rigid containers are also used for transport, while others are more particularly adapted to allow weighing. The maintenance of a flexible bag 1 of 3D type from the outside, in a rigid structure for receiving and holding for storage is known per se, it will not be further described here.

 In the particular embodiment of Figures 1A-1 B and 2, it is understood that the connection port or ports 4, 6 can be placed exclusively in a flap 22 or two flaps 21, 22, defined by the first wall element 2 optionally in the vicinity of a continuous weld 140 of the flexible bag 1 without passing through such a weld 140. This type of configuration is well suited in particular for placing the flexible pouch 1 of the 3D type in a storage device 10 without lateral access to the volume inside.

 With reference to FIGS. 1, 8A and 9, the maximum extension of each bellows 1, 12 caused by filling makes it possible to move the first wall element 2 from the second wall element 3 by a distance D at least equal to 12 or 15 cm, and preferably at least 40 or 50 cm for storage applications in the device 10. It is thus possible to contain, in such a flexible pouch type 3D, a volume of biopharmaceutical product of at least 2 liters, and preferably at least 5 liters.

 Examples of multilayer functional films for constituting the wall elements 2, 3 and the bellows 11, 12 of the flexible bag 1 are known, in particular in the document US2012 / 028039 from the same applicant. These films make it possible to obtain a great flexibility coupled with a satisfactory resistance, which facilitates the unfolding of the bellows 11, 12 without the risk that swelling (during filling) in the first end face W1 or in the side wall W3 causes a break in the film.

The first wall element 2 is typically a flexible piece consisting of a multilayer film and for defining a front face 2a of the flexible bag 1, while the second wall element 3, made in a similar or identical manner (by a multilayer film ) is a flexible piece for defining a rear face 3a of the flexible bag 1, as clearly visible in Figures 1A, 1B and 2. The bellows 11 and 12 may have a material and a similar thickness (preferably identical) to what is provided for the wall elements 2 and 3. It is understood that the bellows 11 and 12 are constituted by respective films cut from one piece, the cutting can take place before, during or after the step of connection with the wall elements 2 and 3.

 Advantageously for filling with a biopharmaceutical fluid 7, the inner layer of each of the films that make up the flexible pouch 1 is made of hot-weldable plastic and biocompatible with the transported media. In a preferred embodiment, each film has a multilayer structure. This multilayer structure can be broken down for example into three layers which are typically non-metallic plastic layers. By way of non-limiting example, the film may be transparent or translucent.

 In a preferred embodiment, the first bellows 11 and the second bellows 12 each have:

 an inner heat-sealable layer of a material selected from polyethylene (preferably linear low density) and ethylene-vinyl acetate copolymer; and

 a weldable outer layer, made of a material chosen from polyethylene (preferably linear low density or possibly high linear density), polyamide, ethylene-vinyl acetate copolymer, polyamide and polyethylene terephthalate.

 The first wall element 2 and the second wall element 3 may have a structure similar or identical to that of the bellows 11, 12. An intermediate layer, for example having a barrier effect (for example based on EVOH or equivalent material ), can be provided in the multilayer structure of the elements 2, 3, 11, 12 defining the volume of the flexible bag 1. The multilayer structure can be broken down into at least three non-metallic plastic layers, and is preferably transparent or translucent.

 Referring now to FIGS. 1A and 6, it will be noted that the bellows 1 and 12 are spaced from one another by a transverse spacing D2. This transverse spacing D2 corresponds to a constant distance in the planar configuration, as clearly visible in FIG. 1A in particular.

The fold lines FL1 and FL2 for the first bellows 1 and the second bellows 12 are then rectilinear and parallel to the lateral edges 8, 18 and 9, 19 defined by the wall elements 2 and 3. It can be seen that the fold lines FL1 and FL2 extend on either side of the longitudinal axis A (in this case a central axis, as clearly visible in Figure 1B) of the flexible bag 1 in the planar configuration. With reference to FIGS. 2 and 8A, which represent the flexible bag 1 in a state filled with biopharmaceutical fluid, the first bellows 11 is connected to two lateral edges 8 and 9 of the first and second wall elements 2 and 3. Similarly, the second bellows 12 is connected to two other lateral edges 18 and 19 of each of the first and second wall members 2 and 3. The connection to the side edges 8, 18 of the first wall element 2 and at the side edges 9, 19 of the second wall element 2 results from a direct weld thus fixing the margin zones of the bellows 11 and 12 which run along the lateral edges 8, 9, 18, 19. following, these margin areas will be called longitudinal edges.

 The first bellows 11 and the second bellows 12 can each bend along their fold line FL1 and FL2, inwardly. In this example the folding is made in two equal halves for each bellows January 1, 12, at least in the planar configuration of the flexible bag 1. Each fold line FL1, FL2 extends between two opposite ends 14, 15 of the flexible pocket 1 where the bellows 11, 12 meet.

 With reference to FIGS. 8B and 8C, it can be seen that the passage to the filled configuration, with a parallelepipedic geometry, is permitted by a narrowing of each bellows 1, 12 in the direction of extension of the fold line FL1 or FL2, due to the swelling to the outside of the side wall W3. The section FL1 'visible in FIGS. 2 and 8A-8B corresponds to a segment of the fold line FL1.

 The unfolded deployment, which would limit the size of this section FL1 ', is obtained more easily thanks to the continuous welding which is carried out to maintain edge portions 11a, 11b, 12a, 12b (FIGS. 2 and 6). bellows 1 1 and 12.

 In this example, there is provided a continuous weld 140 on the side of the first end 14 of the flexible bag 1 and also a continuous weld 150 on the side of the second end 15 (opposite the first end 14). More generally, at least one of the two ends 14, 15 of the flexible bag 1, the first wall element 2 and the second wall element 3 are welded to each other in a transverse direction by a weld continuous 140 and / or 150 which joins perpendicularly (in the plane configuration) the four lateral edges 8, 9 and 18, 19,

FIG. 6 illustrates a detail of a flexible pouch 1 in planar configuration, seen from the end 15. This detail shows more particularly the continuous weld 150 which is made at this end 15. Each portion of the edge portion 11a, 12a is folded in half and wedged between the corresponding ends of the first wall element 2 and the second wall element 3. Of course, this configuration can be reproduced on the opposite side to wedge, by a continuous weld 140, edge portions 11b, 12b of the respective bellows January 1, 12 between the other ends of the wall elements 2 and 3.

 It may be provided to form two flanges at the opposite ends 14, 15, which are welded simultaneously. In order to delimit the ends 14 and 15 of the flexible bag, a post-sealing cutting step of the films is for example provided for separating two solder areas.

 With reference to FIG. 2, the flexible pocket 1 of the 3D type has, for a fully deployed / filled state that corresponds to the parallelepiped configuration:

 - On the side of the first end 14, two first flaps 21, 31, one of which is part of the first wall member 2 and the other part of the second wall member 3; and

 on the side of the second end 15, two second flaps 22, 32 one of which is part of the first wall element 2 and the other part of the second wall element 3.

 The first flaps 21, 31 on the one hand and the two second 22, 32 flaps are made joined by the corresponding welding zone 140, 150. Welded end flanges are thus formed in the form:

 a first protruding strip at the junction of the two first flaps 21, 21; and

a second protruding strip at the junction of the two second flaps 22, 32.

 Comparing FIG. 2 to FIG. 11, which represents a 3D flexible pouch of an existing kind, it can be seen that each of the end faces W1 and W2 shown in FIG. 2 results from the formation of these rectangular flaps 21, 31 and 22, 32 belonging to the two wall elements 2 and 3. For the formation of the end face W2, which is an upper face in this example, the first two flaps 21 and 31 cover the bellows 1 1 from above and 12. These first flaps 21 and 31 of rectangular format tend to limit the deformations related to the flexibility of the material constituting the flexible pouch 1 type 3D.

 More generally, at least one external face W1, W2 of the flexible pouch 1 can be formed in the parallelepipedal configuration by joining two flaps 21, 31 or 22, 32 by welding 140 or 150, forming a strip which protrudes towards the outside. outside relative to the filled volume delimited by the flexible bag 1 (from the outer face of the pocket defined by a pair of flaps 21, 31 or 22, 32).

Here in the case of Figure 2, a first protruding band forming the weld 140 is typically straight / straight and extends parallel to the front face 2a and the rear face 3a. This first protruding band has a substantially straight free edge and is stiffer than the non-welded bag portions. A second protruding band forming the weld 150, which is typically straight / straight, also extends parallel to the front face 2a and the rear face 3a. This second protruding band has a substantially straight free edge and is stiffer than the non-welded bag portions. It is understood that the protruding strip or strips have in a cross section the type of configuration shown in FIG. 6. As a result, each projecting strip has:

 a maximum thickness which is four times greater than the thickness E (FIG. 12) in the flexible zones of the flexible pouch 1 making it possible to vary the internal volume of the pouch 1; and

 a minimum thickness which is twice as great as the thickness E in the flexible zones of the flexible pouch 1 making it possible to vary the internal volume of the pouch 1.

 As clearly visible in FIG. 6, each protruding strip may have a central weld portion CB made directly between an inner face of the first wall element 2 and an inner face of the second wall element. These internal faces are preferably defined by a particular layer (layer on the inside for contact with the biopharmaceutical fluid) of a multilayer structure. The central weld portion CB has an extension (in the direction of extension of the protruding band) which is equal to the transverse spacing D2 between the first bellows 11 and the second bellows 12 in the planar configuration.

 The protruding strip or strips are here more stiffened on either side of the central weld portion CB, due to the increase in thickness due to the edge portions 11a, 11b, 12a, 12b. The stiffened portions RP of each protruding band are elongated portions, longer than the central weld portion CB (measuring along the length of the straight strip, transversely to the longitudinal direction DD of movement), and preferably at least twice as long.

Such elongated RP rigidified portions, which are absent in the conventional 3D soft bags (see FIG. 11) which have a K-weld (KS welds in the case of FIG. 11, which require for each face W1, W2 four weld zones which are neither longitudinal nor transverse), contribute to maintain the rectilinear protruding band and limit the risk of leakage in or at the periphery of the central weld portion CB. With reference to FIG. 2, the welds 140 and 150 are of the same length, so that the opposed protruding strips which define the ends 14, 15 have an identical length (corresponding to the determined dimension L2, here a width).

 As clearly visible in FIGS. 1A-1 B and 2, each flap of the two first flaps 21, 31 and the two second flaps 22, 32 is delimited by a U-shaped weld zone defining two right angles, in particular in the configuration. plane. Each U-shaped weld zone is designed and arranged to prevent, whatever the proportion of filling of the flexible pouch 1:

 a depiiage of a first triangular portion T11 belonging to the first bellows January 1 and adjacent to an edge portion 11a, 1 1b folded in two belonging to the first bellows January 1;

 - unfolding a second triangular portion T12 belonging to the second bellows 12 and adjacent to a portion of edge 12a, 12b folded in two belonging to the second bellows 12.

 The first triangular portions T1 1 and the second triangular portions

T12, which extend substantially in a plane parallel to the end faces W1, W2 in the parallelepipedic configuration, contribute to obtain a flatness of the flaps (21, 31, 22, 32). This is advantageous for filling biopharmaceutical fluid 7 with very large volumes (up to 3000 liters and beyond) without generating folds in the W1, W2 faces that prevent reaching a target volume of biopharmaceutical fluid. Here, each triangular portion T1 1, T12 is formed by the folding of one of the wall members 2 and 3 which is illustrated in Figure 8B, marrying a portion of a flap of this wall member.

 As clearly visible in FIG. 10, under the face W1, four triangular portions T1 1 and T12 extend in the same plane along the flaps 22, 32 in the parallelepipedal configuration. Similarly under the face W2, four triangular portions T1 1 and T12 also extend in the same plane along the flaps 21, 31 in the parallelepiped configuration.

In variants, the flexible pouch 1 shown in FIG. 10 may have the same general configuration with different ports, for example to define a container of the flanged type and allowing agitation, as described in document EP 2 326 412 (see in particular FIGS. 1E to 1H and FIG. 2 in this document). Then we find the wall element 2 which is typically placed on the top and supports the flange (the reverse can be provided with the wall element 2 on the bottom). It can thus be seen that, also when the flexible bag 1 allows stirring / mixing applications, the port or ports are placed away from the welds on at least one of the wall elements 2, 3.

 In embodiments, the juncture between the flaps 21, 31 and 22, 32 results from local heating during a sufficiently long exposure period (which may be of the order of 4 or 6 seconds or possibly 10 seconds per second). example) to heat or heating by a low voltage electrical pulse (for example up to 9 pulses), thanks to a welding head. The technique of heating by a low voltage electric pulse can be used so that the aesthetics of the visible face is unchanged while ensuring a good quality of welding: indeed, it does not require high pressure at the time of welding.

 Impulse welding, thermal welding or laser welding techniques can make it possible to obtain resistant welds 140, 150. In the case of a thermal weld, it is preferable to weld the four films simultaneously by applying a pressure of between 4 and 8 bar between the blades or solder bars SB2. The heating of the solder blade on the outer film belonging to one of the wall elements 2, 3 (plate plated with a pressure of 6 bars for example) is programmed to reach a target temperature, for example of approximately 168 ° C. C or 180 ° C. By way of non-limiting example, the boards are heated to 168 ° C. and the boards are applied by maintaining this temperature on the film for 4 seconds, then the boards are removed. There is no cooling period before removing SB2 solder bars or bars from the film. Heating can start substantially simultaneously with obtaining contact with pressure on the area to be welded.

 These parameters are obviously variable depending on the film and its thickness. However, since the thickness is typically much greater than 100 micrometers, it is preferable to provide an exposure time of at least 2 or 3 seconds, the exposure time being between 3 and 6 seconds.

Of course, the target temperature may vary as the case may be. It is preferred that this temperature be between 150 ° C and 250 ° C. A target temperature between 65 and 190 ° C may be preferred to advantageously reduce the heating time (for example to avoid exceeding 10 seconds), without risk of degrading the outer surface of a wall element 2, 3. Given the the thickness of the films (thickness at least 180 micrometers with several non-metallic layers) and the desired high resistance, the heating time at the target temperature can be here at least 3 or 4 seconds. In the case of a pulse weld, the blades are applied to the film and then the heating is started. The rise in temperature is very fast (less than a second). The temperature of the blades can be raised to a target temperature of between 170 and 190 ° C, for example 180 ° C. This setpoint temperature is maintained for an exposure time which can be between 6 seconds and 10 seconds for example. An exposure time of the order of 5 or 6 seconds or a little more makes it possible to obtain the welding of four layers with a target temperature at 180 ° C. (without this value being limiting). Then the slides are allowed to cool by simply stopping the heating (the current is cut), typically up to 80 ° C or similar threshold. The cooling time may be less than or equal to 50 seconds, and for example between 15 or 20 seconds and 40 seconds. This cooling time can be reduced by using a cooling system of the welding blades (ventilation, circulation of a coolant). Then, the blades or SB2 solder bars are moved aside to disengage them from the film. With reference to FIGS. 3 to 6, an exemplary embodiment of the lateral welds SL which are formed in a longitudinal direction (direction or longitudinal direction DD of travel of the film strips) during the production of the flexible bags is shown. production line, the insertion of the bellows January 1 and 12 can be carried out in a manner known per se (see Figure 3 step 50 of supply and disposition of the films 102, 103, 11 and 1 12, and the step 51 of folding inwards of the films 11, 112 intended to form the bellows

I, 12). In order to weld each bellows 11, 12, the corresponding film 11 can be held in abutment against a guide which has been used for folding or against an equivalent stop element 40 (FIG. 4).

 The step 50 of supplying and disposing of the four films 102, 103, 1 1 and 12 is typically permitted by the use of rollers (not shown) which wind these films in the same general direction, called longitudinal direction DD scrolling. Of course this direction simply serves as a reference for explaining the drawings and it is, of course, possible to route the films with one or more changes of direction (no need that the direction of transport corresponds to a straight line).

It is understood that the films 102, 103, 111 and 1 2, which respectively constitute the first wall element 2, the second wall element 3, the first bellows 11 and second bellows 12, are here welded together defining, in the flat configuration, a total of six welds, including: two solder zones (welds 140, 150) formed at the two opposite ends 14, 15 and which extend in a transverse direction; and

 - Four weld zones perpendicular to the transverse direction, to form the lateral welds SL (which therefore extend parallel to the longitudinal direction DD scrolling).

 Referring to Figure 5, it can be seen that the six welds SL, 140, 150 are continuous and not embrittled by an opening or frangible areas. The width of each of these welds SL, 140, 150 may be at least equal to 5 mm in order to minimize the risk of leakage by an accidental shock.

 At least along the weld zones and in the six welds SL, 140, 150, the thickness of each of the films 102, 103, 111 and 112 is not reduced with respect to the thickness E of said films in the zones away from the welds, the thickness E of these films 102, 103, 111 and 1 2 being typically constant. There is no fringe zone or other weak area to allow an opening.

 By way of non-limiting example, the thickness E (FIG. 12) is a constant thickness or possibly an average thickness, and can be between 90 and 450 μm for each of these films 102, 103, 11 and 112.

 As illustrated by the nonlimiting example of FIG. 3, the four lateral welds SL can be produced simultaneously during a welding step 52 which makes it possible to assemble the four films 102 and 103 (first pair of films facing each other). -vis), 1 1 1 and 1 12 (second pair of films vis-à-vis and conveyed transversely to the first pair of films). The pair of films 102 and 103 makes it possible to form, after a cutting step 53, the respective wall elements 2 and 3, whereas the pair of films 11 1 and 1 12 make it possible to form, after the cutting step 53, the first bellows 11 and the second bellows 2.

 Step 53 of cutting can be optional. The material of the four films 102, 103, 11, 12 is here identical. More generally, it will be understood that the first wall element 2, the second wall element 3, the first bellows and the second bellows 12 are defined by rectangular sheets optionally having the same multilayer structure, with a layer defining an internal face adapted to contact with a biopharmaceutical fluid 7.

With reference to FIG. 4, a pair of solder bars SB1 or similar elements of a welding unit, arranged in a longitudinal direction on a production line, bears from the outside (against the stop element 40) on the side edges 8, 9, 18, 19 of the wall elements 2 and 3 and make it possible to realize side welds SL, here by thermal conduction for a short time (also known as pulse welding). The duration of conductive heating may be less than or equal to 4 or 6 s, given the high temperature and typically greater than 150 ° C, preferably not exceeding 200 ° C for the upper threshold of effective temperature range of the bars of SB1 welding. The welding step 52 is thus carried out by continuously welding the longitudinal edges of the bellows 11 and 12 against the lateral edges 8, 18, 9, 19. Lateral welds SL are made which extend from one to the other. the other of the first and second ends 14, 15, as illustrated in particular in Figure 5.

 Although FIG. 5 illustrates the case of a continuous weld, made for example by pulse, just before a cutting step by a blade of a cutting member 42 which extends transversely with respect to the longitudinal direction DD of scrolling it is also possible to provide a different order of the steps and / or to perform the cutting at another time. It can also be expected to make cuts or pre-cuts before the transverse welds 140, 150.

 Furthermore, it is understood that all the welding steps are performed without prior introduction of material, such as a biopharmaceutical fluid 7, between the four constituent elements 2, 3, 11 and 12 of the flexible bag 1.

 In preferred applications, a filling of the flexible pouch 1 of the 3D type can be performed only after the complete sealing of the flexible pouch 1 and the formation of the connection port or 4, 6. It is understood that the system or systems C1, C2 can be associated, from the design, to the connection ports 4, 6, in order to prevent air from entering the flexible bag 1. Thus, the flexible bag 1 can be proposed empty, without the least orifice permitting ambient air or, alternatively, systematically with connection ports that form an inlet for biopharmaceutical fluid and an outlet (placed on the same side as the inlet) to expel air. This is particularly advantageous for maintaining a biopharmaceutical fluid 7 in a sterile state. The flexible pouches 1 of 3D type shown in Figures 2, 8A, 9 and 10 allow such a maintenance in a sterile state. Preferably, the two opposite ends 14, 15 are designed identically.

In the embodiment shown in Figure 9, the flexible bag 1 has only a continuous weld 150 as wide as the wall elements 2 and 3 to form the face W1 decomposing into two flaps 22 and 33. The face W2 'is differentiates here from the face W1 in that the wall elements 2, 3 have been narrowed in width and the junction between the four elements 2, 3, 1 1, 12 constituting the flexible bag 1 results from a weld K. The advantages of robustness and improved guiding during filling are obtained on the side of the face W1 which is here a lower face and which has a connection port 4 on which is mounted sealingly a flexible pipe 5 to perform a drain.

 FIG. 5 shows an exemplary embodiment of welds 140 and 150, formed transversely in this type of process, here before a cutting step to separate two adjacent pockets. The continuous welds 140 and 150 are made subsequent to the lateral welds SL to complete the sealing of the flexible pouch 1 type 3D. SB2 weld bars or similar elements are distributed on either side of the plane of the pockets to come to heat locally the outer surface of the wall elements 2, 3 opposite. With a system that has four SB2 solder bars, it is possible to simultaneously weld the edges formed at the ends 14 and 15, forming continuous welds 140 and 150 which are as wide as the flexible bags 1 of the 3D type in the planar configuration. .

 In order to obtain the pockets of FIGS. 1A-1 B and 2, this heating has been carried out in the area of overlap of the edge portions 11a and 12a of the two bellows 11, 12 (in order to form the weld 150) and also in the overlap area of the other edge portions 11b and 12b (to form the weld 140). The flexible pouch 1 is closed hermetically on its four sides when it is in the planar configuration, access to the inside of the pouch 1 being only allowed by the connection ports 4, 6 which are formed in a subsequent step (which can vary the position and / or size of the connection ports 4, 6, depending on the desired biopharmaceutical application for the pocket).

 In contrast to what is required to form a K-weld, with the need to accumulate a transverse weld step on the production line and two skew welds followed by an angle cutting step, the manufacturing process is here advantageously simplified with a last simple cutting step which is performed across the longitudinal direction DD scrolling pockets, as clearly visible in Figure 5. Optionally, a single cutting member 42 can achieve all the transverse cuts.

FIGS. 8B and 8C illustrate only a part of each continuous weld 140, 150, which makes it possible to stretch the first bellows 11 between the ends 14 and 14 without generating torsion during filling in: the region R1 of connection between the fold line FL1 and the continuous weld 140; and

 the connection region R2 between the fold line FL1 and the continuous weld 150.

 Of course, the same arrangement is provided for the connection of the fold line FL2 to the continuous welds 140, 150, so that the tendency to torsion in:

 the connecting region R3 (visible in FIGS. 1B and 10) between the fold line FL2 and the continuous weld 140; and

 the connection region R4 (visible in FIGS. 1B and 9) between the fold line FL2 and the continuous weld 150.

 FIGS. 1A-1B and 2 show that the continuous weld 140, 150 extends over the entire width L2 of the respective wall elements 2 and 3. The perimeter defined by these elements 2 and 3 is generally rectangular, possibly square, in the plane configuration. More generally, each continuous weld 140, 150 has a length which coincides with an external dimension (measured in the same direction) of the wall elements 2, 3, both in the planar configuration of the flexible bag and in the parallelepiped configuration.

 With reference to FIG. 2, the distance between the opposite ends 14, 15 which have the welds 140, 150 is typically a length L1 (length common to the wall elements 2, 3 and the bellows 11, 12) which exceeds the width L2 defined by the two wall elements 2 and 3. In addition, the following relationship is typically satisfied:

 0.05 <D2 / L2 / <0.5

where D2 denotes a transverse spacing (minimum distance) between the first bellows and the second bellows, measured in the transverse direction (same direction as for the measurement of the width L2).

Referring to Figures 2 and 8A, filling causes the formation of the front faces 2a and rear 3a. In the parallelepipedic configuration, the flexible pouch 1 then has a common height which corresponds to the height of the front faces 2a and rear 3a. To form the side wall W3, the front face 2a and the rear face 3a are connected by two other faces defined by the unfolding of the bellows 11, 12 (with formation of the section FL1 'on one side and a similar section of the 'other side). These two other faces are delimited each by a pair of longitudinal edges of the bellows 11, 12. A first longitudinal edge of the first bellows 11, continuously welded, is U-shaped and symmetrical shape with a second longitudinal edge of the second bellows 12, also continuously welded and shaped in. U, a rectangular delimitation of a first face F1 (Figure 8A, face F1 defined by the first bellows January 1) of the side wall W3, which connects the front face 2a to the rear face 3a.

 A second intermediate face (defined by the second bellows 12) is also formed in the same way and extends parallel to the first face F1 in the parallelepiped configuration. It may be noted that the longitudinal axis A belongs to a virtual median plane perpendicular to the base of the U-shape, so that the U-shaped longitudinal edge has two halves symmetrical with respect to this median plane.

 The U-shaped configuration of the longitudinal edges has the advantage of better guiding the deployment of the bellows 11, 12, compared with what occurs with a conventional weld in K. Moreover, the substantially straight angle that is formed between the branches of the "U" formed by the longitudinal edges and the base of the "U" avoids, at the lateral welds SL, the torsion effects encountered with a weld K that weaken the seal in the corners of the corresponding faces. While the triangular portions T1 1 and T12 have a right angle (90 °) at the junction of the corresponding lateral weld SL and the continuous weld 140 or 150, the other two angles can be preferably between 30 ° and 60 °. °.

 In order to improve the mechanical strength of the flexible pouch 1, each of the films

102, 103, 1 11, 1 12 can have an assembly 17 of functional layers superimposed on a contact layer 16. With reference to FIG. 12, an outer face made of PET can be provided thanks to the outer layer 17c. This material, which typically has a semi-crystallinity, gives good resistance to oxygen in the air (chemical resistance), low water absorption rate and thus allows long term storage applications. . The thickness of the outer layer 17c may be particularly small, for example between 7 and 50 μηη, preferably between 10 and 30 μιη. Alternatively one can provide a linear high density polyethylene, or other thermoplastics (especially polyamide) which are easily weldable and hard enough to improve the strength of the assembly.

The contact layer 16 may consist of a layer of material compatible with biological materials without deterioration effect. Polyethylene, in particular linear low density polyethylene, is an example of a preferred material for constituting the contact layer 16, since it combines the advantages of compatibility with the biopharmaceutical fluid 7 and good weldability. Other materials to similar properties can be used, for example the ethylene-vinyl acetate copolymer.

 An intermediate layer 17a may correspond to the gas barrier layer (especially with respect to the oxygen and carbon dioxide present in the ambient air). In some options, one or two layers of tacky material (glue layers) may be provided on one side and / or the other of the barrier layer.

 Another intermediate layer 17b may consist of polyamide (PA), which improves the impact resistance (mechanical strength). Here, by way of non-limiting example, the intermediate layer 17b for the mechanical strength is placed between the outer layer 17c and the layer 17a with a gas barrier effect. Due to the lower resistance of the gas barrier layer 17a, it can advantageously be placed between the contact layer 16 and the other layers 1b, 17c of the assembly 17. The composition of the multilayer film shown on FIG. FIG. 12 may be used for all the films 102, 103, 11, 12 of the flexible pouch 1 of the 3D type. Such a composition may make it possible to limit the thickness E to less than 450 μm, for example of the order of 200 or 400 +/- 50 μm. The thickness may be reduced to about 100 +/- 30 μιτι, for example for applications without hermetic closure of the flexible pouch.

 Alternatively, it is possible to use only three layers and to define a set 17 in two layers with greater flexibility. The layers 17b and 17c are replaced by a single layer of polyethylene, preferably linear low density polyethylene. In this case, it is preferable to define a thicker contact layer 16 than in the example illustrated, so that the thickness E is of the order of about 400 +/- 50 pm, for example non-limiting. The material of the contact layer 16 may also be linear low density polyethylene.

 The films preferably have three layers and have a tensile strength typically greater than 60 or 80 Newton. This tensile strength can generally be between 60 and 220 Newton. The flexible pouch 1 is thus particularly difficult to degrade.

The elongation at break, which defines the capacity of each of the films to elongate before breaking (in response to a tensile test), is for example greater than or equal to 80% but less than or equal to 400% or 500%. %. It is understood that the flexible pouch has physical and mechanical properties well suited for the deployment of a folded state flat to a deployed parallelepiped state, which in practice eliminate the risk of accidental tearing. One of the advantages of the flexible pouch 1 of the 3D type is its robustness, particularly in the corners which are reinforced and in the transverse welds, for a method of obtaining which limits the number of welding and cutting steps. The manufacturing process is more easily automated to increase the production rate. In addition the fragilities induced due to the precision of the positioning of the welds at the junctions between the side weld and the fillet welds which must be perfectly opposite the folds of the bellows to obtain a perfect K weld (the least fragile possible ) are deleted.

 Deployment is facilitated for filling thanks to a guiding effect caused by the continuous weld or welds 140, 150, even if the films 102, 103, 11, 112 have a reduced flexibility (this reduced flexibility corresponds for example to a desire to to increase the longevity and / or the mechanical properties of the flexible pouch 1 of the 3D type).

Claims

claims

1. 3D flexible bag (1) to be filled by a biopharmaceutical product (7), preferably using at least one flexible supply line (T1, T2), and provided with at least one connection port (4, 6) for filling and / or emptying, the flexible bag (1) being designed to deploy from a flat vacuum configuration to a substantially parallelepipedic configuration in a filled state, the flexible bag having:

 a first wall element (2) consisting of a film (102) and making it possible to define a front face (2a),

 a second wall element (3) consisting of a film (103) and making it possible to define a rear face (3a),

 a first bellows (1 1) and a second bellows (12), each connected to two lateral edges (8, 9, 18, 19) of one and the other of the first and second wall elements (2, 3); ), the first bellows (11) and the second bellows (12) being constituted by respective films (1 11, 112) cut in one piece and each capable of folding along a fold line inwardly (FL1, FL2) extending between two opposite ends (14, 15) of the flexible pouch (1), and

 said connection port (4, 6) formed exclusively in one of the first wall element (4) and the second wall element (6),

the first wall element (2) and the second wall element (3) being welded to each other in a direction transverse to at least one of the two opposite ends (4, 15),

characterized in that the first wall element (2), the second wall element (3), the first bellows (1 1) and the second bellows (12) are flexible and have a tensile strength of between 60 and 220 Newton,

and wherein the first wall member (2) and the second wall member (3) have in said transverse direction a determined dimension (L2) which is, at least in the planar configuration, substantially the same:

in said front and rear faces (2a, 3a),

 and at least one of the two opposite ends (14, 15), where a continuous weld (140, 150) extends over the entire determined dimension (L2),

said continuous weld (140, 150) further allowing, in the same end (14, 15) of the pocket, to maintain in a folded flat state an edge portion (11a, 11b) of the first bellows (1 1) and an edge portion (12a, 12b) of the second bellows (12), both in the planar configuration and in the parallelepiped configuration.

 The flexible pouch according to claim 1, wherein the first bellows (1 1) and the second bellows (12) are each in a folded state in two in the flat configuration, being folded inwardly along a rectilinear fold line (FL1, FL2), the continuous weld (140, 150) being transverse to the rectilinear fold line (FL1, FL2) in the planar configuration and allowing, in the same end (14, 15) of the pocket flexible (1), to maintain folded in two said edge portion (1 1 a, 1 1 b) of the first bellows (1 1) and said edge portion (12a, 12b) of the second bellows (12), both in the plane configuration and in the parallelepiped configuration.

 Flexible pouch according to claim 1 or 2, comprising a connection port (4, 6) placed in a flap (21, 22) defined by the first wall element (2), on the side of the continuous weld (140, 150) and with a spacing relative to the continuous weld.

 A flexible pouch according to any one of the preceding claims, comprising two first flaps (21, 31), one of which is part of the first wall element (2) and the other part of the second wall element (3). , the first two flaps (21, 31) being joined and forming:

- an outer face (W2) of the flexible bag (1) in the parallelepiped configuration; and

 a first protruding strip which extends parallel to the front face (2a) and to the rear face (3a), provided with a substantially straight free edge, the first protruding band projecting from said outer face (W1) of the flexible pocket in the parallelepipedic configuration, the continuous weld (140) stiffening the entire first protruding band.

The flexible pouch according to claim 4, comprising two second flaps (22, 32), one of which is part of the first wall element (2) and the other part of the second wall element (3), the two second ones. flaps (22, 32) being joined together forming a second protruding strip located opposite the first protruding band and provided with a substantially rectilinear free edge, the second protruding band projecting from another external face (W1) of the flexible pouch, said other external face (W1) being defined by the second flaps (22, 32) in the parallelepipedic configuration, extending parallel to the front face (2a) and the rear face (3a).

The flexible pouch of claim 5, wherein at least one of the first protruding band and the second protruding band:

 - Has a central solder portion (CB) made directly between an inner face of the first wall member (2) and an inner face of the second wall member (3); and

 - Is further stiffened on either side of the central weld portion (CB) in portions (RP) longer than the central weld portion (CB), and preferably at least twice as long.

 The flexible pouch of claim 5 or 6, wherein the first protruding band and the second protruding band have an identical length and each flap of the first two flaps (21, 31) and the second two flaps (22, 32) is defined by a U-shaped weld zone defining two right angles in the planar configuration, each U-shaped weld zone being designed and arranged to prevent, whatever the proportion of filling of the flexible bag (1):

unfolding a first triangular portion (T1 1) belonging to the first bellows (1 1) and adjacent to an edge portion (1 a, 1 1 b) of the first folded bellows;

unfolding a second triangular portion (T12) belonging to the second bellows (12) and adjacent to an edge portion (12a, 12b) of the second bellows folded in two;

the first triangular portion (T1 1) and the second triangular portion (T12) extending substantially in the same plane along a flap chosen from one of the first two flaps (21, 31) and the two second flaps ( 22, 32).

 8. flexible pouch according to any one of the preceding claims, wherein the first bellows (1 1) is defined by two first longitudinal edges which extend from one to the other of the two opposite ends (14, 15). of the flexible pouch (1), while the second bellows is delimited by two second longitudinal edges which extend from one to the other of the two opposite ends (14, 15), knowing that:

 the first two longitudinal edges are continuously welded and each U-shaped in the parallelepipedal configuration, delimiting in a rectangular manner a first face (F1) of the flexible bag which is defined by the first bellows (1 1) in the parallelepipedic configuration; , and

the two second longitudinal edges are continuously welded and each conform in U in the parallelepipedic configuration, delimiting rectangular a second face of the flexible bag which is defined by the second bellows (12) in the parallelepiped configuration.

9. Flexible bag according to any one of the preceding claims, wherein the determined dimension (L2) is identical in the front face (2a), the rear face (2b) and each of said flaps (21, 22, 31, 32). , so that the two first flaps (21, 31) and the two second flaps (22, 32) form by themselves two opposite rectangular faces of the flexible pouch (1) in the parallelepiped configuration and partially cover the first and second bellows (1 1, 12).

 The flexible pouch according to any one of the preceding claims, wherein the films (102, 103, 1 1 1, 1 12) constituting respectively the first wall element (2), the second wall element (3), the first bellows (1 1) and second bellows (12) are welded together defining in the planar configuration a total of six welds (SL, 140, 150), of which:

 two continuous welds (140, 150) formed at the two opposite ends

(14, 15) and which extend in the transverse direction; and

 four lateral welds (SL) perpendicular to the transverse direction.

1 1. A flexible pouch according to claim 10, wherein each of the six welds (SL, 140, 150) is continuous and of a width of at least 5 mm.

 The flexible pouch according to claim 10 or 11, wherein each of the films (102, 103, 11 1, 1 12) respectively constituting the first wall element (2), the second wall element (3), the first bellows (1 1) and the second bellows (12) present locally, along the welds (SL, 140, 150), a thickness which is not less than the average thickness of said films, said average thickness being between 150 and 450 μm for each of these films (102, 103, 11, 1, 12).

 The flexible pouch of any one of the preceding claims, wherein the following relationship is satisfied:

 0.05 <D2 / L2 <0.5

where L2 denotes the determined dimension; and

D2 denotes a transverse spacing between the first bellows and the second bellows, measured in said transverse direction.

14. Flexible pouch according to any one of claims 1 to 13, wherein the films (102, 103, 1 1 1, 1 12) respectively constituting the first wall element (2), the second wall element (3). , the first bellows (1 1) and the second bellows (12), have the same structure being each composed of at least three non-metallic plastic layers, and are preferably transparent or translucent.

 The flexible pouch according to claim 14, wherein the films (102, 103, 1 1 1, 1 12) respectively constituting the first wall element (2), the second wall element (3), the first bellows (1). 1) and the second bellows (12) each have a thickness of between 150 micrometers and 450 micrometers.

 16. A flexible pouch according to claim 14 or 15, wherein the first bellows (1 1) and the second bellows (12) each have:

 - an inner layer (16) heat sealable, a material selected from polyethylene and ethylene-vinyl acetate copolymer; and

 - A weldable outer layer (17c), a material selected from polyethylene, polyamide, ethylene-vinyl acetate copolymer, polyamide and poly (ethylene terephthalate).

 The flexible pouch according to any one of the preceding claims, wherein in the parallelepipedic configuration:

 the maximum extension of each of the first and second bellows (1 1, 12) is at least 15 cm between the first wall element (2) and the second wall element (3); and

 the flexible pouch (1) makes it possible to delimit an interior space at least equal to 2 L, preferably at least equal to 5 L.

 18. A method of manufacturing a 3D flexible pouch (1) to be filled by a biopharmaceutical product (7) defined in any one of the preceding claims, wherein is unwound in a longitudinal direction (DD) of scrolling and transversely cut :

a first wall element (2) provided with two lateral edges (8, 9) consisting of a flexible film and making it possible to define a front face (2a),

 a second wall element (3) provided with two lateral edges (18, 19) consisting of a flexible film and making it possible to define a rear face (3a),

 a first bellows (1 1) and a second bellows (12), each constituted by a flexible film cut in one piece and delimited by two longitudinal edges,

knowing that each of the first bellows (1 1) and the second bellows (12) is inserted, in a folded state in two around a longitudinal fold line (FL1, FL2), between the first wall member (2) and the second wall element (3), the first bellows (1 1) and the second bellows (12) being arranged with transverse spacing (D2) relative to each other; the method further comprising the steps of:

 longitudinally welding the two longitudinal edges of the first bellows (1 1) to the first wall element (2) and to the second wall element (3), respectively to one of the lateral edges (8, 9) of the first wall element (2). ) and the second wall element (3), whereby two first side welds (SL) are obtained;

 longitudinally welding the two longitudinal edges of the second bellows (12) to the first wall element (2) and the second wall element (3), respectively to the other of the lateral edges (18, 19) of the first wall element ( 2) and the second wall element (3), whereby two second lateral welds (SL) are obtained;

 transversely welding the first wall element (2) and the second wall element (3) to form a welded end flange, and preferably two opposite welded end flanges, sandwiching between the first wall element (2) and the second wall element (3), respectively two layers of the first bellows (1 1) folded in two and two layers of the second bellows (12) folded in half, so that the first bellows (1 1) and the second bellows (2) are also welded in an end flange, and preferably two opposite end flanges, perpendicular to their longitudinal edges in a planar configuration of the flexible pouch (1), each longitudinal fold line (FL1 , FL2) extending between two opposite ends (14, 15) of the flexible bag (1) in a flat vacuum configuration, so that the first bellows (1 1) and the second bellows (12) allow the pocket flexible (1) deploys r from the flat vacuum configuration to a parallelepipedal configuration in a filled state, each end flange being continuously welded and defining a determined external dimension (L2) of the flexible pouch (1) which is common to the rear face ( 2a) and the front face (3a) in the parallelepiped configuration;

 - inserting, exclusively in one of the first wall element (2) and the second wall element (3), a connection port (4, 6) for connecting a flexible supply pipe (T1, T2) ;

the first wall element (2), the second wall element (3), the first bellows (1 1) and the second bellows (12) having a tensile strength of between 60 and 220 Newton.

19. The manufacturing method according to claim 18, wherein two parallel opposite end flanges are welded to define the same external dimension. determined (L2) of the flexible bag (1), the first wall member (2) and the second wall member (3) having a rectangular perimeter in the planar configuration.

 20. The manufacturing method according to claim 18 or 19, wherein the first wall element (2), the second wall element (3), the first bellows (1 1) and the second bellows (12) are defined by rectangular sheets having the same multilayer structure.