BAG FOR DISTRIBUTING A PRODUCT FOR BIOPHARMACEUTICAL USE IN THE GENERAL STATE OF A LIQUID OR PASTE VIA A PLURALITY OF OUTLET PORTS

Abstract

A flexible bag for biopharmaceutical use, includes a shell for receiving, in an inner space thereof, a flowable biopharmaceutical product, and flexible walls joined by fixed and sealed rigid-connection areas, two opposite walls being connected to each other by the peripheries thereof, at least one inlet port and one outlet port, a port being combined with a passage of the shell and mounted thereon by fixed and sealed connection elements, a plurality of similar outlet ports grouped together in a tapping area, a tapping wall provided with at least one opening for the passage and assembly of the outlet port for the similar outlet ports, fixed and sealed port-shell connection elements which are rigidly, fixedly, and sealingly connected to the tapping wall around the at least one opening for the passage and assembly of the outlet port, and an area for folding the two opposite walls.

Description

The invention relates to a bag for distributing a product for biopharmaceutical use in the general state of a liquid or paste via a plurality of outlet ports. Its objects, in its various aspects, are the bag in question whether in an unfolded configuration or a folded configuration, a distribution assembly comprising such a bag, a method for making use of such a bag, and a method for creating such a bag.

By convention, “biopharmaceutical product” is understood to mean a flowable product in the general state of a liquid or paste, obtained from biotechnology (culture media, cell cultures, buffer solutions, artificial nutrition liquids) or having a pharmaceutical purpose.

A flexible single-use bag for distributing a biopharmaceutical product via a plurality of outlet ports into containers, such as primary containers, is known from the prior art. Such a known bag firstly comprises a shell able to receive the biopharmaceutical product within its inner space and comprising, joined by fixed and sealed connection areas, flexible walls of which two opposite walls are peripherally connected to each other. It then comprises at least one inlet port by which the inner space can be filled with the biopharmaceutical product. Lastly, it comprises a plurality of outlet ports for simultaneously distributing the biopharmaceutical product located in the inner space, into containers such as primary containers. Such an inlet or outlet port is associated with a passage in the shell and is mounted onto it by fixed and sealed connection means.

For a typical biopharmaceutical use such as the production, storage, or transport of biopharmaceutical product, flexible single-use bags are generally known in which the two walls are directly joined to each other by fixed and sealed connection areas, for example folded, bonded adhesively, or welded, and which, once expanded, have a limited volume, for example 20 liters, and remain relatively thin, which is why they are often referred to as “pillow bags” or “2D bags” (where D stands for dimensional). Also known are flexible 3D single-use bags which comprise two walls joined and securely connected together by means of two welded side gussets, which can be folded flat or unfolded when deployed, the volume then reaching at least 50 liters and up to 3000 liters or more. Such 3D bags are described for example in document WO00/04131 or sold under the trademark FLEXEL® 3D. These 2D or 3D bags comprise fixed and sealed connection areas, at least some of them bonded adhesively or welded, and ports arranged at the connection areas.

For uses such as blood collection and processing or the infusion or collection of parenteral fluid, there are known flexible single-use 2D bags that are of smaller volume (typically 500 ml for example for blood and 50 ml to 3000 ml for infusions) and have inlet and outlet ports arranged at the connection areas by adhesive bonding or welding or at least in the end portion of the expanded bag, as illustrated for example in documents U.S. Pat. No. 3,110,308, U.S. Pat. No. 4,362,158, and U.S. Pat. No. 3,205,889. The invention does not concern these applications.

Document US 2009/0105683 describes a disposable container for biological products, comprising a single sheet of biologically compatible flexible material, an access area wholly molded within said sheet, at least one port in said access area to allow fluid biological materials to be introduced into said container, said sheet being folded along said access area in such a way that an upper portion of said sheet is adjacent to a lower portion of said sheet, and, adjacent to a lower portion of said sheet, a portion connecting said upper portion to said lower portion.

Document FR 2528801 describes a bag for the slow distribution of a liquid medium such as an infusion, having at one end at least one tube at the end opposite a hole for its suspension, and welds closing its side edges, the tubing being attached to a base which adheres to the bag along a fold line from which the opposite walls of the bag extend, this line passing substantially through the geometric axis of each of the tubes.

Document U.S. Pat. No. 4,362,158 describes a bag for human blood and blood fractions, dialysis solutions, infusion solutions, etc., constructed in such a manner that when it is suspended it allows its contents to drain totally or completely, due to an active means in a bellows arrangement.

The present invention relates to a utilization in which a set of p containers, such as similar primary containers of relatively small unit volume, for example from a few milliliters to a few centiliters, are filled with biopharmaceutical product under sterile conditions, from a same single-use flexible bag accepting a larger amount of biopharmaceutical product and having a plurality of n similar outlet ports, the number p of containers being larger as a general rule, possibly much larger, than the number n of outlet ports. In this case, the filling of all p containers is achieved in several passes, the filling being simultaneous in each pass for a number n of containers. In this case, it is generally sufficient for the space inside the bag to have a volume of between 2 and 20 liters, although this range of values is provided purely as a guide.

For such use, it is important that the distribution of biopharmaceutical product by the n outlet ports occurs simultaneously and in an identical manner for the n outlet ports during the use of the bag, particularly with regard to the quality and quantity of biopharmaceutical product distributed. It is also important that at the end of the process, the bag can be entirely or substantially entirely emptied of the biopharmaceutical product that it contained. These aims are difficult to achieve, and may not be achieved, when the bag contains inlet and outlet ports arranged at the connection areas by adhesive bonding or welding. This context and this problem are the basis of the invention.

For an application and a context which are not those of the invention, document U.S. Pat. No. 3,554,256 describes a container for intravenous use which allows adding medications or other ingredients, such as vitamins, to the contents of a container of flexible plastic, in preparation for its administration to a patient. The flexible container for intravenous use has a flexible tubular container member which has each of its ends aseptically sealed. An outlet connector is provided for connecting an intravenous tube, midway between the ends to be connected. The ends of the container member are adapted to be attached to a support stand so that the container member can be folded over at its midpoint and its ends can be readily attached to the support stand, whereby the outlet connector is at the bottom of the container member. At least one additional connector is provided near one of its ends, for adding medications or other ingredients. Initially, one of the ends of the tubular container member is sealed and the other end is left open for filling the container member with intravenous liquid. Then, after filling, this open end is closed. The container according to document U.S. Pat. No. 3,554,256 does not target an application and does not concern a context in which a plurality of p similar primary containers of a relatively small unit volume are filled with a biopharmaceutical product from a single flexible bag for one-time use accepting a larger amount of biopharmaceutical product and having a plurality of n similar outlet ports, the number p of containers being larger, possibly much larger, than the number n of outlet ports. Thus the container according to document U.S. Pat. No. 3,554,256 does not comprise an inlet port for adding content other than one or two ports for adding medications or other ingredients, and has only one outlet port, not multiple ones. Lastly, while the container according to document U.S. Pat. No. 3,554,256 concerns filling the container with added medications or other ingredients, it is not at all concerned with the problem of distributing the contents of the bag through several outlet ports so that this occurs simultaneously and in an identical manner for the various ports, particularly with regard to the quality and quantity of biopharmaceutical product distributed. It also does not concern the problem of the bag being completely empty at the end of the process.

A need therefore exists for single-use flexible bags of the type which comprises: a shell able to receive a biopharmaceutical product within its inner space and comprising flexible walls, joined by fixed and sealed connection areas, of which two opposite walls are peripherally connected to each other; at least one inlet port by which the inner space can be filled with the biopharmaceutical product; and a plurality of n outlet ports for the distribution of the biopharmaceutical product, such that during use of the bag, the distribution of the biopharmaceutical product by the n outlet ports occurs simultaneously and in an identical manner for the different ports, particularly with regard to the quality and quantity of biopharmaceutical product distributed, and such that at the end of the process, the bag can be entirely or substantially entirely emptied of the biopharmaceutical product that it contained.

The purpose of the invention is to provide an answer to this need.

Therefore, in a first aspect, an object of the invention is a bag for distributing a dose of a flowable biopharmaceutical product in the general state of a liquid or paste, into a set of containers, comprising a shell able to receive the biopharmaceutical product in its inner space and comprising flexible walls joined by fixed and sealed connection areas, of which two opposite walls are connected to each other by their peripheries, at least one inlet port by which the inner space can be filled with the biopharmaceutical product, and a plurality of n outlet ports with which are associated in a communicating manner n external discharge/fill tubes, and by which the biopharmaceutical product can be discharged from the inner space into a plurality of containers associated in a communicating manner with the n outlet ports in order to fill them with a dose of biopharmaceutical product, a port being associated with a passage in the shell and being mounted onto it by fixed and sealed connection means.

This bag is such that:

• • the n outlet ports are similar and grouped, in particular near to one another, in a continuous tapping area delimited by the outlet ports or their vicinity, located on a tapping wall of one of the two walls, separate from the connection areas, extending linearly or more widely across a surface area distinctly smaller than the area of the face of the tapping wall,
  • the bag comprises a tapping wall provided with at least one opening for outlet port passage and assembly for the n outlet ports, and fixed and sealed port/shell connection means attached in a fixed and sealed manner to the tapping wall around the at least one opening for outlet port passage and assembly,
  • the bag comprises a folding region of the two walls, at or near where the tapping area is located, where the two walls can be folded onto themselves with the face of the tapping wall being external to the fold while forming an end edge of the folded bag, at or near where the tapping area and the n outlet ports are located.

Thus the bag can be either in an unfolded configuration with the two walls stretched out, or in a folded configuration with the two walls folded onto themselves in the folding region and with the face of the tapping wall being external to the fold, and in which the bag can be filled with biopharmaceutical product, with the end edge arranged and maintained as the lower edge, so that: when the bag is used in the folded configuration, the biopharmaceutical product is discharged simultaneously and in an identical manner through the n outlet ports and the biopharmaceutical product is distributed into the plurality of communicating associated containers in order to fill them with a dose of biopharmaceutical product; this process can be repeated with multiple pluralities of containers; and once the set of containers has been filled with a dose of biopharmaceutical product, the bag can be entirely or substantially entirely emptied of biopharmaceutical product.

In one embodiment, two neighboring outlet ports are spaced apart from each other by a distance chosen so that the flow of biopharmaceutical product through one of the outlet ports does not substantially interfere with the flow of the biopharmaceutical product through the other of the outlet ports.

In some possible embodiments, the tapping area extends over a surface area that is less than ⅕^th particularly less than 1/10^th, even more particularly less than 1/20^th, of the area of the tapping face.

In one characteristic, the tapping area either extends linearly, or linearly but more widely over the surface, along a tapping segment, and in one embodiment, the tapping segment comprises at least one substantially rectilinear section, and, in particular, it is substantially rectilinear.

In one embodiment, the n similar outlet ports are distributed in a manner that is at least substantially uniform over the entire tapping area, and more particularly are spaced apart from each other in a manner that is at least substantially regular.

In one embodiment, the n similar outlet ports are distributed in a more or less substantially uniform manner, in particular are spaced apart from each other in an at least substantially regular manner, throughout the entirety of multiple tapping sub-areas, each tapping sub-area being continuous, delimited by outlet ports or their vicinity, and extending linearly or more widely over the surface, the multiple tapping sub-areas which constitute the tapping area being separated by areas without tapping.

In this embodiment, a tapping sub-area either extends linearly or linearly but more widely over the surface, along a tapping sub-segment, particularly a tapping sub-segment comprising at least one substantially rectilinear section, more particularly being substantially rectilinear and/or extending at least substantially parallel to the tapping segment.

In this embodiment, at least some of the tapping sub-segments, in particular all the tapping sub-segments, are positioned at least substantially parallel to each other or at least substantially as an extension of one another.

In some executions, either an opening for outlet port passage and assembly is associated with a port among the plurality of n outlet ports, or an opening for outlet port passage and assembly is shared by multiple ports among the plurality of n similar outlet ports, or the bag contains a single opening for outlet port passage and assembly shared by the n similar outlet ports.

In one embodiment, an outlet port comprises, associated in a communicating manner, a discharge/fill tube at its proximal end and an attachment plate which is part of the fixed and sealed port/shell connection means and is attached, in particular by adhesive bonding or welding, in a fixed and sealed manner to the tapping wall around an opening for outlet port passage and assembly.

In one embodiment, the discharge/fill tubes are able to be associated in a communicating manner at their distal ends with containers in order to fill them with the biopharmaceutical product, and to be associated functionally with extraction/regulation or discharge shutoff means, in particular programmed or controlled.

In one embodiment, either an attachment plate is associated with an outlet port, or an attachment plate is common to multiple outlet ports, or the bag comprises a single attachment plate common to the n outlet ports.

In one embodiment, the bag comprises as many attachment plates as there are tapping sub-areas, each attachment plate being associated with a tapping sub-area.

In one embodiment, an attachment plate comprises an inside face shaped to facilitate emptying, in particular completely emptying, the biopharmaceutical product.

In one embodiment, the tapping area and/or the folding region is located at or near the middle area of the face of the tapping wall and/or at or near a central axis of the face of the tapping wall between the opposite peripheral sections of the face of the tapping wall.

In one embodiment, no port is located on the face opposite the face of the tapping wall and/or in the connection areas.

In one embodiment, the at least one inlet port is located on the tapping wall at or near the tapping area or at a location separate from the tapping area.

In one embodiment, an inlet port comprises, associated in a communicating manner, a filling/supply tube at its proximal end, able to be associated in a communicating manner at its distal end with a biopharmaceutical product supply, in particular with a filter placed between, and able to be associated functionally with supply/regulation or supply shutoff means, in particular programmed or controlled.

In particular, the bag comprises a plurality of inlet ports, each associated in a communicating manner with a first section of filling/supply tube at its proximal end, said plurality of first sections of filling/supply tubes being associated in a communicating manner at their distal ends with the proximal end of a second common section of filling/supply tube able to be associated in a communicating manner at its distal end with the biopharmaceutical product supply, in particular with a common filter placed between, the supply/regulation or supply shutoff means being associated with the second common section of filling/supply tube.

In one embodiment, the bag additionally comprises at least one gas inlet and/or outlet port.

In one embodiment, the areas of the face of the tapping wall and of the opposite face, both distanced from the folding region and the tapping area, form areas for suspending the bag in its folded configuration, including suspension elements such as holes or projections.

In one embodiment, the bag comprises holding means able to keep the two opposite walls folded onto themselves when the bag is in the folded configuration, including holding elements which complement each other.

In one characteristic, the bag is in an unfolded configuration in which the two opposite walls are stretched out.

In another characteristic, the bag is in a folded configuration in which the two opposite walls are folded onto themselves within the folding region, with the face of the tapping wall being external to the fold, the bag in the folded configuration having, in the folding region, an end edge at or near where the tapping area and the n outlet ports are located.

In one arrangement, the bag comprises means able to maintain constant communication between the two inner sub-spaces located on each side of the folding region.

In one characteristic, the bag is a 2D bag essentially comprising the two flexible walls of the same shape, joined by peripheral connection areas.

In one characteristic, the inner space of the bag has a volume of between 2 liters and 20 liters.

In one embodiment, the bag is sterilized.

In a second aspect, an object of the invention is an assembly for distributing a dose of a flowable biopharmaceutical product in the general state of a liquid or paste, into a set of containers, comprising:

• • a bag for distributing a dose of a biopharmaceutical product and having a folded configuration, in particular a bag in the state of having been filled with biopharmaceutical product,
  • means for holding said bag so that the end edge located at or near the folding region is the lower edge of the bag, the inner space being placed uppermost,
  • means for associating, in a communicating manner, the distal end of the discharge/fill tubes with containers in order to fill them with the biopharmaceutical product located in the inner space of the bag,
  • extraction/regulation or discharge shutoff means, in particular programmed or controlled, associated functionally with the discharge/fill tubes.

In one embodiment, in which the bag is such that an inlet port comprises, associated in a communicating manner, a filling/supply tube at its proximal end, the distribution assembly also comprises means for associating in a communicating manner the distal end of the filling/supply tube with the biopharmaceutical product supply, and supply/regulation or supply shutoff means, in particular programmed or controlled, associated functionally with the filling/supply tube in order to fill the inner space of the bag with the biopharmaceutical product supplied from the biopharmaceutical product supply.

In one embodiment, the extraction/regulation or discharge shutoff means functionally associated with the discharge/fill tubes comprise a pump, such as a peristaltic pump or a pump known as a RDT (Rolling Diaphragm Pump) or similar pump, structurally associated with each discharge/fill tube and regulated to distribute successive doses of biopharmaceutical product, and/or the supply/regulation or supply shutoff means functionally associated with the filling/supply tube comprise a pump structurally associated with the filling/supply tube.

In one embodiment, the distribution assembly also comprises:

• • detection means for detecting that a minimum amount and a maximum amount of biopharmaceutical product has been exceeded in the inner space of the bag,
  • and control means for controlling the extraction/regulation or discharge shutoff means associated with the discharge/fill tubes and the supply/regulation or supply shutoff means associated with the filling/supply tube, responding to said detection means so that when the amount of biopharmaceutical product within the inner space of the bag reaches the minimum amount, the control means order the supply/regulation or supply shutoff means associated with the filling/supply tube to fill the inner space of the bag with the biopharmaceutical product supplied by the biopharmaceutical product supply, and so that when the amount of biopharmaceutical product within the inner space of the bag reaches the maximum amount, the control means order the supply/regulation or supply shutoff means associated with the filling/supply tube to stop filling the inner space of the bag with the biopharmaceutical product supplied by the biopharmaceutical product supply.

In one embodiment, the distribution assembly also comprises:

• • means for providing a plurality, in particular n, containers not yet containing said dose of biopharmaceutical product,
  • means for taking away a plurality, in particular n, containers containing said dose of biopharmaceutical product.

In one embodiment, the containers are located inside an aseptic enclosure and the biopharmaceutical product supply is located outside the aseptic enclosure, the bag being located either inside or outside the aseptic enclosure, the wall of the aseptic enclosure being traversed respectively by either the discharge/fill tubes or by a filling/supply tube.

In a third aspect, the object of the invention is a distribution method making use of a bag for distributing a dose of a biopharmaceutical product as described, for the purposes of distributing a same dose of biopharmaceutical product through the plurality of n outlet ports into p containers, the number p of containers being larger, possibly much larger, than the number n of outlet ports, wherein:

• • a flexible bag having an unfolded configuration as described above is provided,
  • the biopharmaceutical product is provided,
  • p containers not yet containing said dose of biopharmaceutical product are provided,
  • firstly, the bag is folded in its folding region such that the two opposite walls are folded onto themselves with the face of the tapping wall being external to the fold while forming an end edge of the folded bag, at or near which the tapping area and the n outlet ports are located, and thus the bag is placed in its folded configuration as described above; secondly, the inner space of the bag is filled with the biopharmaceutical product via at least one inlet port; thirdly, the n outlet ports are associated in a communicating manner with a first plurality, in particular n, of containers not yet containing said dose of biopharmaceutical product; and fourthly, the end edge is and is maintained so that it is and remains the upper edge of the bag,
  • next, the biopharmaceutical product is discharged through the n outlet ports, simultaneously, and a same dose of biopharmaceutical product is distributed into said first plurality of containers such that a first plurality of containers containing said dose of biopharmaceutical product is obtained,
  • then, while preventing the biopharmaceutical product from discharging through the n outlet ports, said first plurality of containers containing said dose of biopharmaceutical product are removed and a second plurality, in particular n, of containers not yet containing said dose of biopharmaceutical product are provided, and the process is repeated with this second plurality of containers, and so on until the p containers have been filled.

In the embodiments, either the bag is first folded and then the inner space of the bag is filled with the biopharmaceutical product, or the inner space of the bag is first filled with the biopharmaceutical product and then the bag is folded.

In one embodiment, bag holding means are additionally provided and in this embodiment they are put to use so that the end edge of the bag located at or near the folding region is the lower edge of the bag, the inner space being positioned above it.

In one embodiment:

• • on the one hand, the providing means are used to provide a plurality, in particular n, of containers not yet containing said dose of biopharmaceutical product and the distal end of the discharge/fill tubes is associated in a communicating manner with said plurality of containers,
  • on the other hand, the removal means are used to remove a plurality, in particular n, of containers containing said dose of biopharmaceutical product.

In one embodiment:

• • with the detection means, it is detected when a minimum and a maximum amount of biopharmaceutical product located in the inner space is exceeded,
  • and, based on said detection and with the control means, the extraction/regulation or discharge shutoff means associated with the discharge/fill tubes and the supply/regulation or supply shutoff means associated with the filling/supply tube are controlled so that when the amount of biopharmaceutical product within the inner space of the bag reaches the minimum amount, the supply/regulation or supply shutoff means associated with the filling/supply tube are controlled to fill the inner space of the bag with the biopharmaceutical product supplied from the biopharmaceutical product supply, and so that when the amount of biopharmaceutical product within the inner space of the bag reaches the maximum amount, the supply/regulation or supply shutoff means associated with the filling/supply tube are controlled to stop filling the inner space of the bag with the biopharmaceutical product supplied from the biopharmaceutical product supply.

In a fourth aspect, the object of the invention is a method for creating a distribution bag, wherein:

• • a plastic film able to be cut up and attached to itself and to form flexible bag walls is provided,
  • at least one inlet port and a plurality of n outlet ports are provided,
  • film cutting means and attachment means are provided,
  • the film is cut into the shape desired for the walls of the bag, in particular the two opposite walls,
  • at least one opening for outlet port passage and assembly is cut in a tapping wall, for the n outlet ports,
  • and the walls of the bag and the outlet ports are attached in a fixed and sealed manner to the tapping wall around the at least one opening for outlet port passage and assembly.

In one embodiment, at an outlet port (10), a discharge/fill tube is associated in a communicating manner at its proximal end with an attachment plate and the attachment plate is attached, in particular by adhesive bonding or welding, in a fixed and sealed manner to the tapping wall around an opening for outlet port passage and assembly.

In one embodiment, a filling/supply tube is associated in a communicating manner at its proximal end with an inlet port, in particular, the bag comprising a plurality of inlet ports, each is associated with a first section of filling/supply tube at its proximal end, and said plurality of first sections of filling/supply tube are associated in a communicating manner at their distal ends with the proximal end of a second common section of filling/supply tube.

Multiple embodiments of the invention will now be described with the aid of drawings, in which:

FIG. 1 is an elevated view of a single-use flexible 2D distribution bag in the unfolded configuration and in the state where it is empty of biopharmaceutical product, the bag here comprising—purely as an example—six similar outlet ports for biopharmaceutical product with their plates, discharge/fill tubes associated in a communicating manner at their proximal ends with the outlet ports and only partially represented, and extraction/regulation or discharge shutoff means represented here in a purely symbolic manner, two inlet ports, here without a filling/supply tube, located near the tapping area for outlet ports extending linearly over the surface, being closer to the near edge of the tapping wall than the outlet ports, four gas inlet/outlet ports, and two suspension holes, the bag being illustrated from the tapping face side,

FIG. 2 is an elevated view similar to FIG. 1, showing the face of the bag opposite the tapping face,

FIG. 3 is a top view of the bag of FIG. 1,

FIG. 4 is a side view of the bag of FIGS. 1 and 2,

FIG. 5 is an elevated view illustrating a portion of a distribution assembly of the invention, comprising the bag of FIGS. 1 to 4 in the folded configuration with the tapping face being external to the fold, and suspended so that the bag comprises the similar outlet ports and an end edge in the tapping area, the bag being viewed from a first side, the bag being positioned to distribute the biopharmaceutical product to a set of p containers, here a set of p primary containers, the discharge/fill tubes being associated in a communicating manner at their distal ends with these primary containers and being associated functionally with the extraction/regulation or discharge shutoff means which are symbolically represented, as above, the figure also showing means for holding the bag so that the end edge located at or near the folding region is the lower edge of the bag and the inner space of the bag is positioned uppermost,

FIG. 6 is a view similar to FIG. 5, but showing the bag from the second side, opposite the first side,

FIG. 7 is a side view of the distribution assembly and of the bag of FIGS. 5 and 6, when the bag is in the state filled with biopharmaceutical product,

FIGS. 8A and 8B are two simplified schematic views of a 2D bag in the unfolded configuration and in the state empty of biopharmaceutical product, illustrating different possibilities of implementing the similar outlet ports for biopharmaceutical product and the inlet ports: FIG. 8A shows twelve similar outlet ports extending linearly across two sub-areas, arranged parallel and in proximity to one another, and an inlet port distanced from the tapping area but located on the tapping face; and FIG. 8B shows six similar outlet ports in two sub-areas extending across a wider surface and an inlet port located in the tapping area between the two tapping sub-areas,

FIG. 9 is a cross-sectional view on a larger scale, illustrating an outlet port with a section of tube and at its proximal end an attachment plate which is part of the fixed and sealed port/shell connection means, secured in a fixed and sealed manner to the tapping wall around an opening for outlet port passage and assembly,

FIG. 10 is a diagram illustrating a portion of a distribution assembly of the invention, including a distribution bag in the folded configuration and in the filled state, as in FIG. 7, the holding means and the containers (or primary containers) not being represented here, the extraction/regulation or discharge shutoff means functionally associated with the discharge/fill tubes being symbolically represented, the bag having two inlet ports with, associated in a communicating manner, a filling/supply tube at its proximal end, and means for associating in a communicating manner the distal end of the filling/supply tube with a biopharmaceutical product supply, and symbolically represented supply/regulation or supply shutoff means functionally associated with the filing/supply tube.

We will now refer more specifically to FIGS. 1 to 7 and 10 which represent a single-use 2D distribution bag which in general is flexible, specially intended for biopharmaceutical use for distributing a biopharmaceutical product into a set of p containers, such as the p primary containers 2 shown here. Such a bag 1 is intended to be part of, by incorporating it into, a distribution assembly.

“Biopharmaceutical product” is understood to mean a product in the general state of a liquid or paste, meaning it is able to flow, obtained from biotechnology or having a pharmaceutical purpose.

The bag 1 comprises a shell 3 delimiting an inner space 3a suitable for receiving the biopharmaceutical product. This shell 3 comprises, joined by fixed and sealed connection areas 4, two flexible opposite walls 5 and 6, one of which—wall 5—is called the tapping wall, the two walls 5 and 6 facing one another and connected to each other by their peripheral edges 7.

Here the two walls 5 and 6 are of the same general shape and of similar size, such as having an outline that is at least substantially square or rectangular. Such a wall 5 or 6 thus has two pairs of opposite peripheral sections, meaning the pair of sections 7a extending substantially in a same first direction, here forming the small sides (arranged horizontally in the figures), and the pair of sections 7b extending substantially in a same second direction that is orthogonal to the first direction, here forming the large sides (arranged vertically in the figures). The first direction of the sections 7a defines a parallel axis AA which is central on the bag 1 and which, during the use of the bag 1, is positioned horizontally or substantially horizontally, and which is also the axis of a folding region 8 for the walls 5 and 6 and for the bag 1. The sections 7b here define a main axis BB of symmetry of the bag 1, which, during use of the bag 1, is positioned vertically or substantially vertically, and which is also an axis for holding the bag 1 during its use.

In one possible embodiment, the two walls 5 and 6 have a dimension on the order of 10 cm to 50 cm for the small side and 15 cm to 60 cm for the large side.

The embodiment of the two walls 5 and 6 just described is only an example and is not to be considered as limiting. The same is true for the embodiment in which the shell 2 is in the form of a 2D bag.

The inner space 3a of the bag 1 can have a volume of between 2 liters and 20 liters. Such a volume is generally well-suited for uses which involve filling with biopharmaceutical product the plurality of similar primary containers 2, each of a relatively small unit volume, for example on the order of several millimeters to several centiliters.

Such primary containers 2 can be chosen from among a group comprising vials, syringes, flasks, and bottles, with the bags or bag systems possibly but not necessarily being for one-time use. Their unit volume is a fraction of the volume of the inner space 3a of the bag 1.

The flexible walls 5 and 6 of the bag 1 are typically made from single layer or multilayer plastic film, in particular comprising PE, PP, EVOH, etc. They are securely attached in the connection areas 4 by adhesive bonding, or possibly by adhesive bonding or by any other manner. These embodiments are only provided as examples and are not to be considered as limiting. It is therefore possible that in a section 7a, 7b of the peripheral edge 7, the walls 5 and 6 are connected to each other by a fold.

The bag 1 also comprises at least one inlet port 9 and a plurality of n similar outlet ports 10, suitable for emptying the biopharmaceutical product received in the inner space 3a so that the biopharmaceutical product is distributed from the plurality of outlet ports 10, particularly, in this specific application, in order to fill the primary containers 2 of which the number p may be equal to the number n of outlet ports 10, it then being possible to associate each primary container 2 with an outlet port 10 because the outlet ports 10 and the primary containers 2 are placed in communication.

In one embodiment, an appropriate number of primary containers 2 are filled with the contents of one bag 1. In this case, it is possible to close the inlet port 9 once the inner space 3a of the bag is filled with the necessary amount of biopharmaceutical product. In another embodiment, the desired number of primary containers 2 are filled with several successive contents from the same bag 1. In this case, the distribution assembly is adapted as will be described below with reference to FIG. 10.

In the embodiments specifically illustrated in the figures, the bag 1 can comprise a plurality of at least four outlet ports 10, more particularly at least eight outlet ports 10, and even more particularly at least twelve outlet ports 10. In FIG. 10, there are ten outlet ports 10. These numbers are only examples and are not to be considered as limiting. They indicate that the bag comprises not one outlet port but a plurality of greater or lesser magnitude depending on the application, particularly on the number of primary containers 2 to be filled, at least to be filled during each pass through the filling process.

Where required, the bag 1 comprises other ports able to carry out a function other than emptying and distributing biopharmaceutical product.

In the embodiments of FIGS. 1 to 7, the bag 1 additionally comprises one or more gas inlet and/or outlet ports 11.

In the embodiment in FIGS. 1 to 7 and 10, the outlet ports 10 for the bag 1 consist of the plurality of n similar outlet ports 10, excluding the gas inlet and/or outlet ports.

A port 9, 10, 11 is associated with an appropriate passage in the shell 3 and is mounted onto the shell by fixed and sealed attachment means.

The ports 10 of the plurality of n similar outlet ports 10 are grouped in a tapping area 12. “Grouped” is understood to mean the fact that the outlet ports 10, located near each other, are all within the tapping area 12. Thus the tapping area 12 establishes the boundary within which the outlet ports 10 are located, this boundary being adjacent to the outlet ports 10 or located at a short, and in particular a very short, distance from the outlet ports 10. “Adjacent” here is understood to mean in the immediate vicinity or adjoining. “Located at a short distance” is understood to mean a distance of about a centimeter for walls 5 and 6 having dimensions on the order of 10 cm to 60 cm, as indicated above. It is understood that these numbers are examples only and are not to be considered as limiting. They express that the tapping area 12 does not extend for more than a short distance beyond the outlet ports 10.

In combination with the above arrangement, two outlet ports 10 that are near to each other are spaced apart from each other by a distance suitable to prevent the flow of biopharmaceutical product through one of the outlet ports 10 from substantially interfering with, or even not interfering at all with, the flow of the biopharmaceutical product through the other of the outlet ports 10. Thus, the discharge of biopharmaceutical product through the different outlet ports 10 and the filling of the primary containers 2 can occur simultaneously and in an identical manner.

The tapping area 12 is continuous and is delimited by the outlet ports 10 or their vicinity. It should be understood from this that the tapping area 21 establishes the boundary within which the outlet ports 10 are located, this boundary being adjacent to the outlet ports 10 or located at a short, and in particular a very short, distance from the outlet ports 10. “Adjacent” here is understood to mean in the immediate vicinity or adjoining. “Located at a short distance” is understood to mean a distance of about a centimeter for walls 5 and 6 having dimensions on the order of 10 cm to 60 cm as indicated above. It is understood that these numbers are examples only and are not to be considered as limiting. They express that the tapping area 12 does not extend for more than a short distance beyond the outlet ports 10.

The tapping area 12 defined in this manner is not necessarily identified as such on the bag 1.

The tapping area 12 is located on the tapping wall 5 while being separate from the connection areas 4. Therefore the outlet ports 10 are also located on the tapping wall 5, and no outlet port 10 is located in the connection areas 4. In addition, no outlet port 10 is located on the face 4 opposite the tapping face 5. As a result, the tapping wall 5 is equipped with at least one opening for outlet port 10 passage and assembly 14, for the n similar outlet ports 10.

In one embodiment, these characteristics of outlet ports 10 also apply to the other inlet ports 9 and gas inlet/outlet ports 11.

The tapping area 12 extends linearly or extends more widely over a surface area that is distinctly smaller than that of the tapping face 5. “Extends linearly” is understood to mean that the tapping area is essentially a line or a line segment, possibly having a certain thickness, which extends along a tapping segment. “Extends more widely over a surface” is understood to mean that the tapping area is essentially a surface, in contrast to a line or a segment, itself having a certain thickness. In one embodiment, the tapping area 12 extends linearly but more widely over a surface. “Extends linearly but more widely over a surface” is understood to mean that the tapping area is a surface but it extends substantially along a line or line segment, which itself extends along a tapping segment 13. In the embodiments represented in FIGS. 1 to 7, such a tapping segment 13 is substantially rectilinear. In other embodiments, the tapping segment 13 comprises at least one substantially rectilinear section.

The area of the tapping area 12 extending over a “distinctly smaller” surface area than the area of the tapping face 5, is understood to mean that the area of the tapping area 12 is less than ⅕^th of the area of the tapping face 5, more particularly is less than 1/10^th, even more particularly is less than 1/20^th.

A port 10 is associated with and mounted on the shell 3 by fixed and sealed connecting means 15, secured in a fixed and sealed manner to the tapping area 5 around the at least one opening for outlet port 10 passage and assembly 14.

We will now refer more specifically to FIG. 9, which shows that an outlet port 10 comprises, associated in a communicating manner, a discharge/fill tube 16 at its proximal end 16a towards the shell 3, and an attachment plate 17 which is a part of the fixed and sealed connecting means 15. The discharge/fill tube 16 has a distal end 16b. The tube 16 is said to be a “discharge/fill” tube because it both drains the inner space 3a and fills the primary containers 2. In the embodiment considered, this is a flexible tube which can follow a more or less convoluted path depending on the geometric constraints of the space where it is located (see FIG. 10), and it can be locally flattened when so required in order to cooperate with a shutoff device such as a pinch valve (for example a Halkey-Roberts valve, well known to a person skilled in the art), or a displacement/regulation device or extraction/regulation device, such as a pump, for example a peristaltic pump or a pump known by the acronym RDP for Rolling Diaphragm Pump or a functionally similar pump. This device or unit is denoted by the reference 21 and is represented in a purely symbolic manner. The attachment plate 17 is in effect secured in a fixed and sealed manner to the tapping wall 5 around an opening for outlet port 10 passage and assembly 14. For this purpose, the attachment plate 17 extends over the tapping wall 5 around an opening for outlet port 10 passage and assembly 14 and is secured to the tapping wall 5 in a fixed and sealed manner by adhesive bonding or welding or by any other means assuring both mechanical resistance and fluid-tightness, without creating any obstacle to the flow of biopharmaceutical product. Depending on the embodiment, the attachment plate 17 is attached by its outside face to the inside face of the tapping wall 5 (FIG. 9), with the inside face 17a of the attachment plate 17 being free, or conversely the attachment plate 17 is secured by its inside face 17a to the outside face of the tapping wall 5. The words “inside” and “outside” respectively refer to what is inside or turned towards the inner space 3a, and what is outside or facing away from the inner space 3a. The embodiment specifically described and represented concerning the discharge/fill tube 16 is only an example and is not to be considered as limiting. The various tubes may or may not have the same length, the goal being that they deliver the same dose of biopharmaceutical product. The discharge/fill tubes 16 have a length that is more or less large or more or less small, depending on requirements. Although the embodiment with flexible tubes is advantageous, particularly for satisfying the objectives of physical structure and pinching to flatten, it does not exclude others, the means associated with the tubes 16 then being adapted accordingly, which lies within the reach of a person skilled in the art.

The attachment plate 17 comprises an opening 17b which is a through-hole communicating on the internal side with the inner space 3a, and on the opposite, external, side with the passage formed by the section of tube 16. The attachment plate 17 thus has a generally annular shape, or pseudo-annular or multi-annular if it contains several openings 17b.

The above embodiments of the fixed and sealed connecting means 15 are only provided as examples and are not to be considered as limiting.

For some embodiments and requirements, an inlet port 9 does not have an associated tube (FIGS. 1 to 6, 8A, 8B) or, similarly to the outlet port 10 and as illustrated in FIG. 10, is associated in a communicating manner with a filling/supply tube 25, at its proximal end 25a. The tube 25 is said to be a “filling/supply” tube because it both fills the inner space 3a and supplies the biopharmaceutical product. This filling/supply tube 25 can be associated in a communicating manner at its distal end 25b with a supply 26 of biopharmaceutical product, such as a tank of high storage capacity. A filter 27 may be inserted on the filling/supply tube 25. The filling/supply tube 25 may also be arranged so that it can be functionally associated, and is functionally associated, with supply/regulation or supply shutoff means 28. These means 28 are represented in a purely symbolic manner in FIG. 10. Depending on the embodiments, these may involve a pinch valve able to close off the filling/supply tube 25 by flattening/pinching it, or a pump, such as a peristaltic pump or a RDP pump or a functionally similar pump. In particular, such means 28 may be programmed or controlled.

More specifically, in the embodiment in FIG. 10 where the bag 1 comprises two inlet ports 9, each of them is associated in a communicating manner with a first section 29a of filling/supply tube 25 at its proximal end 25a. The two first sections 29a of filling/supply tube 25 are associated in a communicating manner at their distal ends 29a with the proximal end 30a of a second common section 30 of filling/supply tube 25 able to be associated in a communicating manner at its distal end 25b with the supply 26. In this case, the filter 27 and the supply/regulation or supply shutoff means 28 are, in the example represented in the figure, associated with the second common section 30.

This embodiment of the inlet port 9 is particularly suitable. In the embodiment already described in which the desired number of primary containers 2 are filled with several successive contents from the same bag 1, which is reloaded with biopharmaceutical product each time it becomes necessary when it has been emptied during distribution into the primary containers 2.

What has been described and indicated concerning the structure of the discharge/fill tubes 16 can also apply to the filling/supply tube or tubes 25.

The bag 1 also comprises the folding region 8 for the two opposite walls 5 and 6.

“Folding region” is understood to mean an area where the walls of the bag 1 can be reshaped so that they are folded onto themselves, in order to have two thicknesses of pairs of walls 5 and 6, each thickness comprising the two walls 5 and 6. It is understood that the edge 18 of the fold of the folding region 8 can be more or less pronounced, ranging from a fairly crisp straight line to a simple rounded curve, in this specific case with a bulge as illustrated in FIGS. 7 and 10. This folding region 8 is, however, specifically located and has a smaller area than the area of the tapping face 5. “Smaller” is understood to mean on the order of ¼^th.

This embodiment of the folding region 12 is only an example and is not to be considered as limiting.

The tapping area 12 is located at or near the folding region 8. This is understood to mean that the two areas 8 and 12 are superimposed, at least substantially, or that the two areas 8 and 12 are adjacent or are located at a short, in particular a very short, distance from each other. “Adjacent” is understood here to mean in immediate proximity or touching. “Located at a short distance” is understood here to mean a distance on the order of a centimeter for walls 5 and 6 having dimensions on the order of 10 cm to 60 cm, as indicated above. It is understood that these numbers are only examples and are not to be considered as limiting. They express that the tapping area 12 is combined with the folding region 12 although the two areas do not have the same surface area, or that the two areas are very close to each other.

At the folding region 8, the two opposite walls 5 and 6 may be folded onto themselves, as described above, with the tapping face 5 located on the outside of the fold formed by the folding region 12. The edge 18 of the fold of the folding region 12 forms an end edge 18 of the bag 1 in its folded configuration (FIGS. 5 to 7).

The tapping area 12 and the n similar outlet ports 10 are located at or near the end edge 18. This is understood to mean that the tapping area 12 and the outlet ports 10 and the end edge 18 are superimposed, at least substantially, or that they are adjacent or located at a short, and in particular a very short, distance from each other. “Adjacent” is understood to mean in immediate proximity or touching. “Located at a short distance” is understood here to mean a distance on the order of a centimeter for walls 5 and 6 having dimensions on the order of 10 cm to 60 cm, as indicated above. It is understood that these numbers are only examples and are not to be considered as limiting. They express that the tapping area 12 and the n similar outlet ports 10 are part of the end edge 18 of the bag 1 in its folded configuration, or that they are very close to each other.

The above embodiments of the folding region 12 are only examples and are not to be considered as limiting.

FIGS. 1 to 7 illustrate a first embodiment, in which the n similar outlet ports 10 are distributed in a manner that is at least substantially uniform and are spaced apart from each other in a manner that is at least substantially regular throughout the tapping area 12.

FIGS. 8A and 8B illustrate a second embodiment, in which the n similar outlet ports 10 are distributed in a manner that is at least substantially uniform, not throughout the entire tapping area 12 as in the first embodiment, but throughout multiple tapping sub-areas, in this case two sub-areas 12a and 12b. This embodiment is only an example and is in no way limiting, as the number of sub-areas 12a, 12b . . . may be different.

Each tapping sub-area 12a, 12b . . . has the characteristics of the tapping area 12, meaning it is continuous, delimited by outlet ports 10 or their vicinity, and extends linearly (FIG. 8A) or more widely over the surface (FIG. 8B) and in particular extends linearly or extends linearly but more widely over the surface of a tapping sub-segment 13a, 13b . . . (FIG. 8A). In the embodiment represented in FIG. 8A, such tapping sub-segments 13a, 13b are substantially rectilinear. In other embodiments, one or more tapping sub-segments 13a, 13b comprises at least one substantially rectilinear section.

In the embodiment in FIG. 8A, the tapping sub-segments 13a and 13b are positioned to be at least substantially parallel to each other. In another embodiment, the tapping sub-segments 13a, 13b . . . are at least substantially an extension of one another.

In addition, in the embodiment of FIG. 8A, the tapping sub-segments 13a and 13b extend at least substantially parallel to the tapping segment 13. In another embodiment, a tapping sub-segment 13a, 13b extends at least substantially parallel to the tapping segment 13.

In the embodiment in FIG. 8B, the two sub-areas 12a and 12b placed at a distance from each other along the segment 13 of the tapping area 12.

The characteristics described above for the folding region 12 can apply to each tapping sub-area 12a, 12b . . . . Thus the outlet ports 10 can be spaced apart from each other in at least a substantially regular manner in each tapping sub-area 12a, 12b. . . .

The different sub-areas 12a, 12b . . . constituting the entire tapping area 12 are separated from each other by areas with no tapping 19. “Area with no tapping” 19 is understood to mean that in this area there is no tapping for outlet ports 10, which does not exclude the presence of some other port, such as for example an inlet port 9 as represented in FIG. 8A.

Where required, at least some of the tapping sub-areas 12a, 12b . . . , in particular all the tapping sub-areas 12a, 12b . . . , are located near one another.

In the embodiment in FIG. 8A, there are two sub-areas 12a and 12b extending linearly, arranged opposite one another, parallel to one another, and neighboring one another. This embodiment allows the lower end edge 18 of the bag 1 to be placed in its folded configuration between the two sub-areas 12a and 12b, parallel to the sub-sections 13a and 13b.

In the embodiment in FIG. 8A, there are two sub-areas 12a and 12b extending over the surface, along the segment 13 of the tapping area 12, at a distance from one another, leaving between them an area with no tapping 19 in which the inlet port 9 is located.

The embodiments described are only provided as examples and are not to be considered as limiting the number, shape, and relative arrangement of the sub-areas 12a, 12b . . . , or the number and relative arrangement of the outlet ports 10 in each sub-area.

The arrangement of at least one opening for outlet port 10 passage and assembly 14 will now be described in relation to the outlet ports 10.

In the embodiment in FIGS. 1 to 7, there is only one opening for passage and assembly 14, shared by the plurality of n similar outlet ports 10. Such an arrangement is well-suited for cases where the n similar outlet ports 10 are distributed throughout the tapping area 12, which is a single area without sub-areas, in the sense described above.

In another embodiment, it can be arranged so that an opening for passage and assembly 14 is shared not by the plurality of n similar outlet ports 10, as above, but only by a portion of the outlet ports 10 among the plurality of n similar outlet ports 10. Such an arrangement is well-suited for cases where the tapping area 12 comprises several tapping sub-areas 12a, 12b. . . . Thus as many openings for outlet port 10 passage and assembly can be provided as there are tapping sub-areas 12a, 12b. . . . In this case, each opening for outlet port 10 passage and assembly 14 is associated with a tapping sub-area 12a, 12b. . . . In the case in FIGS. 8A and 8B, two openings for passage and assembly 14a and 14b corresponding to the two sub-areas 12a and 12b are arranged.

In the embodiment in FIG. 9, a single outlet port 10 among the plurality of n similar outlet ports 10 is associated with an opening for outlet port 10 passage and assembly.

The embodiments described concerning the arrangement of the opening for outlet port 10 passage and assembly 14 are only examples and are not to be considered as limiting.

Now the arrangement of an attachment plate 17 will be described in relation to one, some, or all the outlet ports 10.

In the embodiment in FIGS. 1 to 7, a single attachment plate 17 common to the plurality of n similar outlet ports 10 is provided. Such an arrangement is well-suited for cases where the n similar outlet ports 10 are distributed throughout the entire tapping area 12, which is a single area without sub-areas, in the sense described above.

In another embodiment, an attachment plate 17 is common not to the plurality of n similar outlet ports 10, as above, but only to a portion of the outlet ports 10 among the plurality of n similar outlet ports 10. Such an arrangement is well-suited for cases where the tapping area 12 comprises several tapping sub-areas 12a, 12b . . . . There can thus be as many attachment plates 17 as there are tapping sub-areas 12a, 12b . . . . In this case, each attachment plate 17 is associated with a tapping sub-area 12a, 12b . . . . In the case in FIGS. 8A and 8B, two attachment plates 17 corresponding to the two sub-areas 12a and 12b are provided.

In the embodiment in FIG. 9, an attachment plate 17 is associated with a single outlet port 10 among the plurality of n similar outlet ports 10.

Depending on the embodiments and on whether an attachment plate 17 is arranged relative to one, some, or all the outlet ports 10, an attachment plate 17 comprises a single opening 17b for the n similar outlet ports 10 or an opening 17b shared not by the plurality of n similar outlet ports 10, as above, but by only a portion of the outlet ports 10 among the plurality of n similar outlet ports 10, or an opening 17b is associated with a single outlet port 10 among the plurality of n similar outlet ports 10. Where necessary, the attachment plate can comprise a middle portion in grid form and a solid peripheral portion for the attachment and for the fixed and sealed connection.

The embodiments described concerning the arrangement of an attachment plate 17 in relation to one, some, or all the outlet ports 10 and the arrangement of the opening or openings 17a are only provided as examples and are not to be considered as limiting.

In one embodiment, the attachment plate 17 has a certain rigidity, which gives a certain resistance to the section of tube 16. In another embodiment illustrated in FIG. 9, the inside face 17a or the free central portion of the inside face 17a around the passage provided in the attachment plate 17 is shaped to facilitate the emptying, and in particular the complete emptying, of the biopharmaceutical product. For example, the inside face 17a may be funnel-shaped or may contain drainage channels.

The discharge/fill tube 16 is designed to be able to be associated in a communicating manner at its distal end 16b with a primary container 2 to be filled with the biopharmaceutical product that is in the bag 1. In one embodiment, the discharge/fill tube 16 comprises, at its distal end 16b, a nozzle 20 or a similar distribution device such as filling needles. This association is designed to be detachable, so that the distal end 16b is separated from the primary container 2 when it is filled, then associated with another primary container 2 to be filled, and so on.

The distribution assembly can also comprise means for associating/dissociating nozzles 20 or similar distribution devices fitted onto the discharge/fill tubes 16. These means may be wholly or partially manual or mechanized, programmed where applicable to work in concert with the operation or programmed sequence of filling and providing and removing primary containers 2.

For this purpose, the distribution assembly also comprises means for providing, on the one hand, a plurality, particularly n, of containers not yet containing the desired dose of biopharmaceutical product, and on the other hand, means for removing a plurality, in particular n, of containers containing said dose of biopharmaceutical product. These means may be wholly or partially manual or mechanized, programmed where applicable to work in concert with the operation or programmed sequence of filling.

As already indicated, the distribution assembly also comprises a shutoff means (such as a pinch valve) or a displacement/regulation or extraction/regulation device (such as a pump, for example a peristaltic pump or a RDP pump or a functionally similar pump) 21 with which each discharge/fill tube 16 cooperates. Such means 21 can be programmed or controlled according to the filling desired and the conditions and procedures for doing so.

In one embodiment, the means 21 are not specific to each of the discharge/fill tubes 16 but are common to multiple tubes 16.

The embodiments described concerning the attachment plates 17 and the tube section 16 are only examples and are not to be considered as limiting.

Now the various configurations and states of the flexible distribution bag 1 will be described.

The distribution bag 1 is, when required, in an unfolded configuration (FIGS. 1 to 4) in which the two opposite walls 5 and 6 are stretched out. In this configuration, the bag 1 is, when required, either in an empty state where the inner space 3a is empty of biopharmaceutical product (FIGS. 1 to 4)—for example once the flexible bag 1 has been created—or in a filled state where the inner space 3a is filled with biopharmaceutical product—for example in a first variant of the use of the flexible bag 1.

The distribution bag 1 is, when required and in order to be used for emptying the biopharmaceutical product located in the inner space 3a, in a folded configuration (FIGS. 5 to 7) in which the two opposite walls 5 and 6 are folded onto themselves in the folding region 8 with the tapping face 5 being external to the fold. In this folded configuration, the distribution bag 1 comprises, in the folding region 8, an end edge 18 at or near where the tapping area 12 and the n similar outlet ports 10 are located. In this folded configuration, the distribution bag 1 is, when required, either in a filled state where the inner space 3a is filled with biopharmaceutical product (FIGS. 5 to 7)—for example at the moment when the bag is to be emptied—or in an empty or emptied state, where the inner space 3a is respectively empty or emptied of biopharmaceutical product—for example before filling the flexible bag with biopharmaceutical product in a second variant of its use or after emptying, respectively.

The arrangement of the tapping area 12 and the folding region 8 on the tapping face 5 will now be described.

As a result, it is important that the tapping area 12—which is not necessarily identified as such on the bag 1—and the folding region 8 are positioned judiciously on the tapping face 5. In the embodiment in FIGS. 5 to 7, the tapping area 12 and the folding region 8 are located at or near the middle region 5b of the tapping face 5. For example, the tapping area 12 and the folding region 8 are located at or near the central axis AA of the tapping face 5 positioned at equal distances from the two opposite peripheral sections 7a of the tapping face 5. With such an embodiment, the bag 1 in its folded configuration has a general symmetrical arrangement relative to a vertical plane of symmetry P (parallel to the plane of the FIGS. 5 and 6 and identified in FIG. 7). The inner space 3a is thus subdivided into two inside sub-spaces 3aa and 3ab, of equal or substantially equal volumes. The two peripheral sections 7a are coincident or substantially coincident and constitute the edge of the upper end 22 of the bag 1 in its folded configuration (FIGS. 5 to 7).

In one arrangement, the flexible bag 1 comprises means able to maintain constant communication between the two inside sub-spaces 3a, 3b. These means may be spacers or may consist of allowing gas to escape as the bag 1 is emptied of biopharmaceutical product.

These embodiments are only examples and are not to be considered as limiting.

The arrangement of the inlet port or ports 9 relative to the shell 3 will now be described.

In the embodiment in FIGS. 1 to 6, the flexible bag 1 comprises two inlet ports 9 located on the tapping wall near the tapping area 12, located here on each side of the tapping area 12 but closer to the nearest large peripheral section 7b of the tapping wall 5 than the outlet ports 10.

In the embodiment in FIG. 8B, the flexible bag 1 comprises a single inlet port 9 located at the same location as the tapping area 12, here between the two tapping sub-areas 12a and 12b.

This type of arrangement allows filling the inner space 3a with the biopharmaceutical product while the flexible bag 1 is in its folded configuration; the biopharmaceutical product is injected into the two inside sub-spaces 3aa and 3ab, by the lower end 18 of the bag 1, which prevents the foaming that would occur with a biopharmaceutical product that would foam when injected into the flexible bag by the top.

In the embodiment in FIG. 8A, the flexible bag 1 comprises a single inlet port 9 located at a location separate from the tapping area 12, and more particularly at a distance from the tapping area 12, for example located at or near an attachment section near the peripheral section 7b, while being located on the tapping wall 5.

In the embodiment in FIG. 10, two inlet ports 2 are arranged halfway up the bag in its folded configuration.

These embodiments concerning the arrangement—number and placement—of the inlet port or ports 9 are only examples and are not to be considered as limiting.

Now the arrangement of the gas inlet/outlet ports 11 will be described.

One or more ports 11 are provided to allow either introducing a gas for preserving this product, from outside the flexible bag 1 into the inner space 3a above the biopharmaceutical product, or for releasing gas from the inner space 3a to outside the flexible bag 1 as it empties which prevents the bag 1 from closing in on itself which could interfere with the emptying of biopharmaceutical product.

One or more such ports 11 are located at a distance from the tapping area 12, and in particular at a definite distance, for example at or near an attachment section near the peripheral section 7a.

In some embodiments, such a port 11 is located on the tapping wall 5 or on the wall 6 opposite the tapping wall 5.

These embodiments concerning the arrangement—number and placement—of the gas inlet/outlet ports 11 are only examples and are not to be considered as limiting.

In one arrangement, the areas 5a and 6a of the tapping face 5 and of the opposite face 6 which are adjoining the section 7a of the bag 1 and which, in the flexible bag 1 in its folded configuration, are adjoining the upper end edge 22 and are opposite the lower end edge 18, form regions for suspending the bag 1 in its folded configuration. Such suspension regions 5a and 6a may include suspension arrangements 23, such as holes or projections able to cooperate in a detachable manner with complementary suspension means, such as hooks or brackets which are part of the machine or system in which the bag is used when emptying it and filling primary containers 2. Such a detachable suspension arrangement with holes or projections 23 and hooks or brackets 23a is part of the general knowledge of a person skilled in the art concerning the bags considered here. In another embodiment, the suspension arrangements 23 are only placed on one of the faces 5 or 6, as long as there are holding means which keep the two opposite walls 5 and 6 folded onto themselves when the bag 1 is in the folded configuration. With suspension means 23 and 23a as described, the flexible bag 1 in its folded configuration is positively held so that the end edge 18 of the bag 1 located at or near the folding region 8 and the tapping area 12 is the lower edge of the bag 1 and so that the inner space 3a is positioned above this, to allow the biopharmaceutical product to empty from the inner space 3a through the outlet ports 10.

Instead of holding means which keep the flexible bag 1 folded in this manner and which are provided in the form of the suspension means 23 and 23a described above, there may be equivalent means for holding the bag which are structurally different but provide the same function. For example, this can be a rigid container comprising in its lower portion at least one passage for the n similar outlet ports, of a shape corresponding to that of the bag filled with biopharmaceutical product. Such a container may incorporate side plates which press against the faces 5 and 6.

The invention includes an assembly comprising a flexible bag 1 as described, means for keeping the flexible bag 1 in its folded configuration such that the end edge 18 is positioned horizontally and downwards and the end edge 22 is positioned horizontally and upwards, the bag 1 being positioned vertically with its plane of symmetry P being vertical. It is thus possible for the biopharmaceutical product to empty through the outlet ports 10 due to gravity, or where necessary in a forced manner and assisted by exerting compression on the two faces 5 and 6 of the bag 1.

Thus, depending on the case, the holding means are suspension means 23b able to cooperate with suspension elements 23a of the bag or side restraining means, such as a rigid container comprising at least one passage for the n similar outlet ports in its lower portion.

These embodiments concerning the holding and in particular the suspension of the flexible bag 1 are only examples and are not to be considered as limiting.

In another development, the flexible bag 1 comprises holding means 24 able to keep the two opposite walls 5 and 6 folded onto themselves when the bag 1 is in the folded configuration, preventing the bag from unfolding.

These holding means 24 can consist of the suspension elements 23 of the bag 1, the suspension of the bag 1 on the complementary suspension elements 23a being such that the two peripheral sections 7a of the bag 1 are kept adjacent or in contact with each other. This effect is obtained due to the weight of the bag 1 on the complementary suspension elements 23a via the suspension elements 23 of the bag 1. Where necessary, the complementary suspension elements 23a are equipped with notches or projections that prevent the two peripheral sections 7a of the bag 1 from moving apart unexpectedly.

These holding means 24 may be holding elements which complement each other, arranged on the shell 3 and in particular on the face 6 which is inside the fold of the bag 1 in its folded configuration. Such complementary holding elements provide reversible or irreversible retention depending on the intended applications and they may be, for example, in the form of self-adhering strips such as snap fasteners or those known under the VELCRO® trademark.

These embodiments concerning the holding of the bag 1 in the folded state are only examples and are not to be considered as limiting.

A flexible bag as described above is most often intended to be used in a sterile environment, and for this reason it is sterile, having been made sterile by appropriate treatment such as, for example, y radiation. Such sterilization treatment of a single-use bag is part of the general knowledge of a person skilled in the art.

The creation of a bag 1 as described can be deduced from the structure of the bag itself.

In this method, plastic film is provided that can be cut up and firmly attached to itself and can form the flexible bag walls that constitute the shell 3, in particular the walls 5 and 6.

Also provided are components for constructing the ports 9 and 11 and especially the similar outlet ports 10.

Also provided are film cutting means and attachment means, in particular sealing means.

Then the film is cut into the shape desired for the walls of the bag, particularly the two opposite walls 5 and 6.

The opening(s) for the passage and assembly 14, 14a, 14b . . . of the n similar outlet ports 10 are also cut in the tapping wall 5.

Next, the walls 5 and 6 are attached to each other in a fixed and sealed manner to form the shell 3 and the outlet ports 10 are attached to the tapping wall 5 in a fixed and sealed manner around the opening or openings 14, 14a, 14b. . . .

This results in a flexible bag 1 as described, in its unfolded configuration and in the state empty of biopharmaceutical product.

In a particular embodiment of the method, a discharge/fill tube 16 is associated in a communicating manner at its proximal end 16a with an outlet port 10 and an attachment plate 17 and the attachment plate 17 is attached in a fixed and sealed manner, in particular by adhesive bonding or welding, to the tapping wall 5 around an opening for outlet port 10 passage and assembly 14.

In one embodiment which can be combined with the previous one, a filling/supply tube 25 is associated in a communicating manner at its proximal end 25a with an inlet port 9. In particular, as the bag 1 comprises a plurality of inlet ports 9, each of them is associated with a first section of filling/supply tube 29 at its proximal end 25a, and the plurality of first sections of filling/supply tube 29 is associated in a communicating manner at their distal ends 29a with the proximal end 30a of a second common section of filling/supply tube 30.

These forms of executing the method for holding the bag 1 are only examples and are not to be considered as limiting.

Another object of the invention is a distribution assembly, for distributing a dose of a biopharmaceutical product into a set of containers 2, such as primary containers 2.

This distribution assembly comprises a distribution bag 1 as has been described, which is for one-time use and in particular is in a state filled with biopharmaceutical product.

The distribution assembly also comprises the means for holding the bag 1, such as the suspension elements 23a, or any other device or arrangement obtaining the same result, meaning that the end edge 18 positioned at or near the folding region 8 is the lower edge of the bag 1, the inner space 3a being positioned uppermost.

The distribution assembly also comprises means for associating the distal end 16b of the discharge/fill tubes 16 with the primary containers 2 in a communicating manner.

The distribution assembly also comprises the extraction/regulation or discharge shutoff means 21 already mentioned.

In one possible embodiment, the distribution assembly may also comprise means which associate, in a communicating manner, the distal end 25b of the or of each filling/supply tube 25 with a supply 26 of biopharmaceutical product.

In this case, the distribution assembly may comprise supply/regulation or supply shutoff means 28, in particular programmed or controlled, functionally associated with the filing/supply tube(s) 25, in order to fill the inner space 3a of the bag 1 with the biopharmaceutical product coming from the supply 26 of biopharmaceutical product.

As indicated, the extraction/regulation or discharge shutoff means 21 may comprise a shutoff pinch valve or a pump regulated to distribute successive doses of biopharmaceutical product. The supply/regulation or supply shutoff means 28 may comprise a pump, such as a peristaltic pump or a RDP pump or another functionally similar pump.

In one embodiment of the distribution assembly, adapted for the case where the p primary containers 2 are filled with several successive bag 1 contents, the distribution assembly is adapted accordingly and first of all is arranged so that it comprises detection means for detecting that a minimum amount and a maximum amount of biopharmaceutical product in the inner space 3a of the bag 1 has been exceeded.

Secondly, this distribution assembly contains means for controlling the extraction/regulation or discharge shutoff means 28 in response to said detection means. Thus, when the amount of biopharmaceutical product within the inner space 3a of the bag 1 reaches the minimum amount, the control means order the supply/regulation or supply shutoff means associated with the filling/supply tube 25 to fill the inner space 3a of the bag 1 with the biopharmaceutical product supplied by the supply 26 of biopharmaceutical product. Then, when the amount of biopharmaceutical product within the inner space 3a of the bag 1 reaches the maximum amount, the control means order the supply/regulation or supply shutoff means 28 to stop filling the inner space 3a of the bag 1 with the biopharmaceutical product supplied by the supply 26 of biopharmaceutical product.

In one arrangement, the primary containers 2 are respectively positioned inside and outside an aseptic enclosure. Depending on the case and on the embodiments, the bag 1 itself is positioned either inside or outside this aseptic enclosure. The wall of the aseptic enclosure is thus traversed respectively either by the discharge/fill tubes 16 or by a filling/supply tube 25.

The method for making use of such a flexible bag 1 is now described, namely the distribution of biopharmaceutical product. In effect, “making use” is understood to mean the act of, starting with a flexible bag 1 in its unfolded configuration and in a state empty of biopharmaceutical product, distributing biopharmaceutical product through the plurality of n similar outlet ports 10, and in particular distributing the biopharmaceutical product into the p primary containers 2.

Initially, a flexible bag 1 in its unfolded configuration and in the empty state is provided. Also provided is some of the biopharmaceutical product.

Also provided are p primary containers 2 which do not yet contain the desired dose of biopharmaceutical product.

First of all, the bag is folded in its folding region 8 so that the two opposite walls 5 and 6 are folded onto themselves with the face of the tapping wall 5 being external to the fold, forming an end edge 19 of the folded bag, at or near where the tapping area 12 and the n outlet ports 10 are located. The bag is thus placed in its folded configuration.

Secondly, the inner space 3a of the bag is filled with the biopharmaceutical product via the at least one inlet port 9.

Thirdly, the n outlet ports 10 are associated in a communicating manner with a first plurality, in particular n, of primary containers 2 not yet containing the desired dose of biopharmaceutical product, particularly by means of nozzles 20.

Fourthly, the end edge 22 is and is maintained so that it is and remains the upper edge of the distribution bag 1 and this is done by means of the suspension elements 23a, more generally the holding means for the bag 1, utilized so that the end edge 18 of the bag 1 positioned at or near the folding region 8 is its lower edge, the inner space 3a being positioned above it.

In this situation, the discharge of the biopharmaceutical product through the n outlet ports 10 and the n associated discharge/fill tubes 16 can be performed in a simultaneous manner at the desired moment, and a same dose of biopharmaceutical product can be distributed into the first plurality of primary containers 2 by the nozzles 20, through the combined effect of gravity and the means 21 (performing a regulation and advancement function). Thus a first plurality of primary containers 2 containing said desired dose of biopharmaceutical product is obtained.

Then, while preventing the biopharmaceutical product from discharging through the n outlet ports 10 by using the means 21 (performing a shutoff function), the first plurality of primary containers 2 which at that time contain the dose of biopharmaceutical product is removed, and a second plurality, in particular n, of primary containers 2 not yet containing the dose of biopharmaceutical product are brought in using the providing and removal means of the distribution assembly.

The process is repeated with this second plurality of primary containers 2, and repeated again, until the p primary containers 2 are filled.

Depending on the embodiments, either the bag 1 is first folded and then the inner space 3a of the bag 1 is filled with the biopharmaceutical product, or the inner space 3a of the bag 1 is first filled with the biopharmaceutical product and then the bag 1 is folded.

In both cases, when the bag 1 is in the folded configuration and in the filled state, the end edge 18 is and is maintained horizontal and downwards and the end edge 22 is positioned horizontally and upwards, the bag 1 being positioned vertically with its plane of symmetry P being vertical.

The method just described was for the case where it is carried out in multiple passes, each time for a number n of primary containers 2, the set of p primary containers 2 concerned being larger, in particular much larger, than n.

Of course, the method can concern the case where p=n.

Moreover, the method can have two variants.

In a first variant, the inner space 3a of the bag is filled with the amount necessary to fill all of the p primary containers 2. These can then be filled with the contents of a single bag 1. In this case, once the inner space 3a of the bag 1 has been filled with biopharmaceutical product, there is no need to reload it with biopharmaceutical product. This is why the inlet port 9 can remain closed.

In a second variant, the inner space 3a of the bag is filled with an amount which is only a fraction of what is required to fill all of the p primary containers. In this case, the p primary containers 2 are filled with several successive bag 1 contents. In a preferred mode, this involves several successive contents from the same bag 1. In this case, and due to the distribution assembly being adapted appropriately, first the detection means comprised in the distribution assembly detects when a minimum amount and a maximum amount of biopharmaceutical product inside the inner space 3a of the bag 1 have been exceeded.

Second, as a function of the detection made and with the control means comprised in the distribution assembly, the extraction/regulation or discharge shutoff means 21 associated with the discharge/fill tubes 16 and the supply/regulation or supply shutoff means 28 associated with the filling/supply tube(s) 25 are controlled so that, when the amount of biopharmaceutical product in the inner space 3a of the bag 1 reaches the minimum amount, the supply/regulation or supply shutoff means 28 associated with the filling/supply tube(s) 25 are controlled so that the inner space 3a of the bag 1 is filled with the biopharmaceutical product supplied from the biopharmaceutical product supply, and when the amount of biopharmaceutical product in the inner space 3a reaches the maximum amount, the supply/regulation or supply shutoff means 28 are controlled so that the filling of the inner space 3a with the biopharmaceutical product supplied from the supply 26 is stopped.

Claims

1-35. (canceled)

36. A bag (1) for distributing a dose of a flowable biopharmaceutical product in the general state of a liquid or paste, into a set of containers (2), comprising a shell (3) able to receive the biopharmaceutical product in its inner space (3a) and comprising flexible walls joined by fixed and sealed connection areas (4), of which two opposite walls (5 and 6) are connected to each other by their peripheries (7), at least one inlet port (9) by which the inner space (3a) can be filled with the biopharmaceutical product, and a plurality of n outlet ports (10) with which are associated in a communicating manner n external discharge/fill tubes, and by which the biopharmaceutical product can be discharged from the inner space (3a) into a plurality of containers (2) associated in a communicating manner with the n outlet ports (10) in order to fill them with a dose of biopharmaceutical product, a port (9, 10) being associated with a passage in the shell (3) and being mounted onto it by fixed and sealed connection means (15), characterized in that:

the n outlet ports (10) are similar and grouped, in particular near to one another, in a continuous tapping area (12) delimited by the outlet ports (10) or their vicinity, located on a tapping wall (5) of one of the two walls (5 and 6), separate from the connection areas (4), extending linearly or more widely across a surface area distinctly smaller than the area of the face of the tapping wall (5),

the bag (1) comprises a tapping wall (5) provided with at least one opening for outlet port passage and assembly (14) for the n outlet ports (10), and fixed and sealed port/shell (3) connection means (15) attached in a fixed and sealed manner to the tapping wall (5) around the at least one opening for outlet port passage and assembly (14),

the bag (1) comprises a folding region (8) of the two walls (5 and 6), at or near where the tapping area (12) is located, where the two walls (5 and 6) can be folded onto themselves with the face of the tapping wall (5) being external to the fold while forming an end edge (18) of the folded bag, at or near where the tapping area (12) and the n outlet ports (10) are located.

37. The bag (1) according to claim 36, wherein it has either of the following elements:

two neighboring outlet ports (10) are spaced apart from each other by a distance chosen so that the flow of biopharmaceutical product through one of the outlet ports (10) does not substantially interfere with the flow of biopharmaceutical product through the other of the outlet ports (10),

the tapping area (12) extends over a surface area that is less than ⅕th, particularly less than 1/10th, even more particularly less than 1/20th, of the area of the face of the tapping wall (5),

the tapping area (12) either extends linearly, or linearly but more widely over the surface, along a tapping segment (13), in particular a tapping segment (13) comprising at least one substantially rectilinear section, more particularly being substantially rectilinear,

the n outlet ports (10) are distributed in a manner that is at least substantially uniform manner over the entire tapping area (12), and in particular are spaced apart from each other in a manner that is at least substantially regular.

38. The bag (1) according to claim 36, wherein the n outlet ports (10) are distributed in an at least substantially uniform manner, in particular are spaced apart from each other in an at least substantially regular manner, throughout the entirety of multiple tapping sub-areas (12a, 12b), each tapping sub-area (12) being continuous, delimited by outlet ports (10) or their vicinity, and extending linearly or more widely over the surface, the multiple tapping sub-areas (12a, 12b) which constitute the tapping area (12) being separated by areas without tapping (19); and optionally wherein a tapping sub-area (12a, 12b) either extends linearly or linearly but more widely over the surface, along a tapping sub-segment (13a, 13b), particularly a tapping sub-segment (13a, 13b) comprising at least one substantially rectilinear section, more particularly being substantially rectilinear and/or extending at least substantially parallel to the tapping segment (13); and even more optionally wherein at least some of the tapping sub-segments (13a, 13b), in particular all the tapping sub-segments (13a, 13b), are positioned at least substantially parallel to each other or at least substantially as an extension of one another.

39. The bag (1) according to claim 36, wherein either an opening for outlet port (10) passage and assembly (14) is associated with an outlet port (10) among the plurality of n outlet ports (10), or an opening for outlet port (10) passage and assembly (14) is shared by multiple outlet ports (10) among the plurality of n outlet ports (10).

40. The bag (1) according to claim 36, wherein an outlet port (10) comprises, associated in a communicating manner, a discharge/fill tube (16) at its proximal end (16a) and an attachment plate (17) which is part of the fixed and sealed port/shell (3) connection means (15) and is attached, in particular by adhesive bonding or welding, in a fixed and sealed manner to the tapping wall (5) around an opening for outlet port (10) passage and assembly (14); and wherein it has optionally either of the following elements:

the discharge/fill tubes (16) are able to be associated in a communicating manner at their distal ends (16b) with containers (2) in order to fill them with the biopharmaceutical product, and to be associated functionally with extraction/regulation or discharge shutoff means (21), in particular programmed or controlled,

either an attachment plate (17) is associated with an outlet port (10), or an attachment plate (17) is common to multiple outlet ports (10), or the bag (1) comprises a single attachment plate (17) common to the n outlet ports (10),

an attachment plate (17) comprises an inside face (17a) shaped to facilitate emptying, in particular completely emptying, the biopharmaceutical product.

41. The bag (1) according to claim 36, wherein it has either of the following elements:

the tapping area (12) and/or the folding region (8) is located at or near the middle area (5b) of the face of the tapping wall (5) and/or at or near a central axis (AA) of the face of the tapping wall (5) between the opposite peripheral sections (7a) of the face of the tapping wall (5);

no port is located on the face (6) opposite the face of the tapping wall (5) and/or in the connection areas (4),

the at least one inlet port (9) is located on the tapping wall (5) at or near the tapping area (12) or at a location separate from the tapping area (12).

42. The bag (1) according to claim 36, wherein an inlet port (9) comprises, associated in a communicating manner, a filing/supply tube (25) at its proximal end (25a), able to be associated in a communicating manner at its distal end (25b) with a biopharmaceutical product supply (26), in particular with a filter (27) placed between, and able to be associated functionally with supply/regulation or supply shutoff means (28), in particular programmed or controlled; and optionally comprising a plurality of inlet ports (9), each associated in a communicating manner with a first section (29) of filling/supply tube (25) at its proximal end (25a), said plurality of first sections (29) of filling/supply tube (25) being associated in a communicating manner at their distal ends (29a) with the proximal end (30a) of a second common section (30) of filling/supply tube (25) able to be associated in a communicating manner at its distal end (25b) with the biopharmaceutical product supply (26), in particular with a common filter (27) placed between, the supply/regulation or supply shutoff means (28) being associated with the second common section (30) of filling/supply tube (25).

43. The bag (1) according to claim 36, wherein it has either of the following elements:

it additionally comprises at least one gas inlet and/or outlet port (11),

the areas (5a et 6a) of the face of the tapping wall (5) and of the opposite face, both distanced from the folding region (8) and from the tapping area (12), form areas for suspending the bag (1) in its folded configuration, including suspension elements (23) such as holes or projections.

44. The bag (1) according to claim 36, wherein it comprises holding means (24) able to keep the two opposite walls (5 and 6) folded onto themselves when the bag is in the folded configuration, including holding elements which complement each other.

45. The bag (1) according to claim 36, having an unfolded configuration in which the two opposite walls (5 and 6) are stretched out.

46. The bag (1) according to claim 36, having a folded configuration in which the two opposite walls (5 and 6) are folded onto themselves within the folding region (8), with the face of the tapping wall (5) being external to the fold, the bag in the folded configuration having, in the folding region (8), an end edge (18) at or near where the tapping area (12) and the n outlet ports (10) are located.

47. An assembly for distributing a dose of a flowable biopharmaceutical product in the general state of a liquid or paste, into a set of containers, comprising:

a bag (1) for distributing a dose of a biopharmaceutical product, having a folded configuration according to claim 46, in particular a bag in the state of having been filled with biopharmaceutical product,

means (23a) for holding said bag (1) so that the end edge (18) located at or near the folding region (8) is the lower edge of the bag, the inner space (3a) being placed uppermost,

means for associating, in a communicating manner, the distal end (16b) of the discharge/fill tubes (16) with containers (2) in order to fill them with the biopharmaceutical product located in the inner space (3a) of the bag (1),

extraction/regulation or discharge shutoff means (21), particularly programmed or controlled, associated functionally with the discharge/fill tubes (16).

48. The distribution assembly according to claim 47, wherein it has in addition either of the following elements:

the bag (1) is such that an inlet port (9) comprises, associated in a communicating manner, a filling/supply tube (25) at its proximal end (25a), said assembly also comprising means for associating in a communicating manner the distal end (25b) of the filling/supply tube (25) with the biopharmaceutical product supply (26), and supply/regulation or supply shutoff means (28), in particular programmed or controlled, associated functionally with the filling/supply tube (25) in order to fill the inner space (3a) of the bag (1) with the pharmaceutical product supplied from the biopharmaceutical product supply (26),

the extraction/regulation or discharge shutoff means (21) functionally associated with the discharge/fill tubes (16) comprise a pump structurally associated with each discharge/fill tube (16) and regulated to distribute successive doses of biopharmaceutical product, and/or the supply/regulation or supply shutoff means (28) functionally associated with the filling/supply tube (25) comprise a pump structurally associated with the filling/supply tube,

the distribution assembly also comprises:

detection means for detecting that a minimum amount and a maximum amount of biopharmaceutical product has been exceeded in the inner space (3a) of the bag (1),

and control means for controlling the extraction/regulation or discharge shutoff means (21) associated with the discharge/fill tubes (16) and the supply/regulation or supply shutoff means (28) associated with the filling/supply tube (25), responding to said detection means so that when the amount of biopharmaceutical product within the inner space (3a) of the bag (1) reaches the minimum amount, the control means order the supply/regulation or supply shutoff means (28) associated with the filling/supply tube (25) to fill the inner space (3a) of the bag (1) with the biopharmaceutical product supplied by the biopharmaceutical product supply, and so that when the amount of biopharmaceutical product within the inner space (3a) of the bag (1) reaches the maximum amount, the control means order the supply/regulation or supply shutoff means (28) associated with the filling/supply tube (25) to stop filling the inner space (3a) of the bag (1) with the biopharmaceutical product supplied by the biopharmaceutical product supply (26),

the containers (2) are located inside an aseptic enclosure and the biopharmaceutical product supply is located outside the aseptic enclosure, the bag (1) being located either inside or outside the aseptic enclosure, the wall of the aseptic enclosure being traversed respectively by either the discharge/fill tubes (16) or by a filling/supply tube (25).

49. A distribution method making use of a bag (1) for distributing a dose of biopharmaceutical product, for the purposes of distributing a same dose of a biopharmaceutical product through a plurality of n outlet ports (10) into p containers (2), the number p of containers being larger, possibly much larger, than the number n of outlet ports (10), wherein:

a flexible bag (1) having an unfolded configuration according to claim 45 is provided,

the biopharmaceutical product is provided,

p containers (2) not yet containing said dose of biopharmaceutical product are provided,

firstly, the bag (1) is folded in its folding region (8) so that the two opposite walls (5 and 6) are folded onto themselves with the face of the tapping wall (5) being external to the fold while forming an end edge (18) of the folded bag, at or near which the tapping area (12) and the n outlet ports (10) are located, and thus the bag (1) is placed in its folded configuration; secondly, the inner space (3a) of the bag (1) is filled with the biopharmaceutical product via at least one inlet port (9); thirdly, the n outlet ports (10) are associated in a communicating manner with a first plurality, in particular n, of containers (2) not yet containing said dose of biopharmaceutical product; and fourthly, the end edge (22) is and is maintained so that it is and remains the upper edge of the bag (1),

next, the biopharmaceutical product is discharged through the n outlet ports (10), simultaneously, and a same dose of biopharmaceutical product is distributed into said first plurality of containers (2) such that a first plurality of receptacles (2) containing said dose of biopharmaceutical product is obtained,

then, while preventing the biopharmaceutical product from discharging through the n outlet ports (10), said first plurality of containers (2) containing said dose of biopharmaceutical product are removed and a second plurality, in particular n, of containers (2) not yet containing said dose of biopharmaceutical product are provided and the process is repeated with this second plurality of containers (2), and so on until the p containers (2) have been filled, the method comprising optionally either of the following elements:

either the bag (1) is first folded and then the inner space (3a) of the bag (1) is filled with the biopharmaceutical product, or the inner space (3a) of the bag (1) is first filled with the biopharmaceutical product and then the bag (1) is folded,

bag (1) holding means (23a) are additionally provided and wherein they put to use so that the end edge (18) of the bag (1) located at or near the folding region (8) is the lower edge of the bag (1), the inner space (3a) being positioned above it,

with the detection means, it is detected when a minimum amount and a maximum amount of biopharmaceutical product in the inner space (3a) of the bag (1) is exceeded,

and, based on said detection and with the control means, the extraction/regulation or discharge shutoff means (21) associated with the discharge/fill tubes (16) and the supply/regulation or supply shutoff means (28) associated with the filing/supply tube (25) are controlled so that when the amount of biopharmaceutical product within the inner space (3a) of the bag (1) reaches the minimum amount, the supply/regulation or supply shutoff means (28) associated with the filling/supply tube (25) are controlled to fill the inner space (3a) of the bag (1) with the biopharmaceutical product supplied from the biopharmaceutical product supply (26), and so that when the amount of biopharmaceutical product within the inner space (3a) of the bag (1) reaches the maximum amount, the supply/regulation or supply shutoff means (28) associated with the filling/supply tube (25) are controlled to stop filling the inner space (3a) of the bag (1) with the biopharmaceutical product supplied from the biopharmaceutical product supply (26).

50. A method for creating a distribution bag (1) according to claim 45, wherein:

a film of plastic material able to be cut up and attached to itself and to form flexible bag walls is provided,

at least one inlet port (9) and a plurality of n outlet ports (10) are provided,

film cutting means and attachment means are provided,

the film is cut into the shape desired for the walls of the bag, in particular the two opposite walls (5 and 6),

at least one opening for outlet port (10) passage and assembly (14) is cut in a tapping wall (5), for the n outlet ports (10),

and the walls of the bag and the outlet ports (10) are attached in a fixed and sealed manner to the tapping wall (5) around the at least one opening for outlet port (10) passage and assembly (14); the method of creation comprising optionally either of the following elements:

at an outlet port (10), a discharge/fill tube (16) is associated in a communicating manner at its proximal end with an attachment plate (17) and the attachment plate is attached, in particular by adhesive bonding or welding, in a fixed and sealed manner to the tapping wall (5) around an opening for outlet port (10) passage and assembly (14),

a filling/supply tube is associated in a communicating manner at its proximal end with an inlet port (9), in particular, the bag (1) comprising a plurality of inlet ports (9), each is associated with a first section of filling/supply tube at its proximal end, and said plurality of first sections of filling/supply tube are associated in a communicating manner at their distal ends with the proximal end of a second common section of filling/supply tube.

51. The bag (1) according to claim 37, wherein the n outlet ports (10) are distributed in an at least substantially uniform manner, in particular are spaced apart from each other in an at least substantially regular manner, throughout the entirety of multiple tapping sub-areas (12a, 12b), each tapping sub-area (12) being continuous, delimited by outlet ports (10) or their vicinity, and extending linearly or more widely over the surface, the multiple tapping sub-areas (12a, 12b) which constitute the tapping area (12) being separated by areas without tapping (19); and optionally wherein a tapping sub-area (12a, 12b) either extends linearly or linearly but more widely over the surface, along a tapping sub-segment (13a, 13b), particularly a tapping sub-segment (13a, 13b) comprising at least one substantially rectilinear section, more particularly being substantially rectilinear and/or extending at least substantially parallel to the tapping segment (13); and even more optionally wherein at least some of the tapping sub-segments (13a, 13b), in particular all the tapping sub-segments (13a, 13b), are positioned at least substantially parallel to each other or at least substantially as an extension of one another.

52. The bag (1) according to claim 37, wherein either an opening for outlet port (10) passage and assembly (14) is associated with an outlet port (10) among the plurality of n outlet ports (10), or an opening for outlet port (10) passage and assembly (14) is shared by multiple outlet ports (10) among the plurality of n outlet ports (10).

53. The bag (1) according to claim 37, wherein an outlet port (10) comprises, associated in a communicating manner, a discharge/fill tube (16) at its proximal end (16a) and an attachment plate (17) which is part of the fixed and sealed port/shell (3) connection means (15) and is attached, in particular by adhesive bonding or welding, in a fixed and sealed manner to the tapping wall (5) around an opening for outlet port (10) passage and assembly (14); and wherein it has optionally either of the following elements:

the discharge/fill tubes (16) are able to be associated in a communicating manner at their distal ends (16b) with containers (2) in order to fill them with the biopharmaceutical product, and to be associated functionally with extraction/regulation or discharge shutoff means (21), in particular programmed or controlled,

either an attachment plate (17) is associated with an outlet port (10), or an attachment plate (17) is common to multiple outlet ports (10), or the bag (1) comprises a single attachment plate (17) common to the n outlet ports (10),

an attachment plate (17) comprises an inside face (17a) shaped to facilitate emptying, in particular completely emptying, the biopharmaceutical product.

54. The bag (1) according to claim 37, wherein it has either of the following elements:

the tapping area (12) and/or the folding region (8) is located at or near the middle area (5b) of the face of the tapping wall (5) and/or at or near a central axis (AA) of the face of the tapping wall (5) between the opposite peripheral sections (7a) of the face of the tapping wall (5);

no port is located on the face (6) opposite the face of the tapping wall (5) and/or in the connection areas (4),

the at least one inlet port (9) is located on the tapping wall (5) at or near the tapping area (12) or at a location separate from the tapping area (12).

55. The bag (1) according to claim 37, wherein an inlet port (9) comprises, associated in a communicating manner, a filing/supply tube (25) at its proximal end (25a), able to be associated in a communicating manner at its distal end (25b) with a biopharmaceutical product supply (26), in particular with a filter (27) placed between, and able to be associated functionally with supply/regulation or supply shutoff means (28), in particular programmed or controlled; and optionally comprising a plurality of inlet ports (9), each associated in a communicating manner with a first section (29) of filling/supply tube (25) at its proximal end (25a), said plurality of first sections (29) of filling/supply tube (25) being associated in a communicating manner at their distal ends (29a) with the proximal end (30a) of a second common section (30) of filling/supply tube (25) able to be associated in a communicating manner at its distal end (25b) with the biopharmaceutical product supply (26), in particular with a common filter (27) placed between, the supply/regulation or supply shutoff means (28) being associated with the second common section (30) of filling/supply tube (25).