EP2645981B1 - Bag for distributing a product for biopharmaceutical use in the general state of a liquid or paste via a plurality of outlet ports - Google Patents

Description

The invention relates to a dispensing bag via a plurality of output ports of a product for biopharmaceutical use in the general state of liquid or pasty. According to its various aspects, its subject is the pocket in question, whether it is in an unfolded configuration or in a folded configuration, a dispensing assembly comprising such a pocket, a method for implementing such a pocket. and finally a method of producing such a pocket.

By convention, the term "biopharmaceutical product" is intended to mean a product in the general liquid or pasty state, suitable for flow, derived from biotechnology (culture media, cell cultures, buffer solutions, artificial nutrition liquids) or having a pharmaceutical purpose.

It is known from the state of the art a single-use flexible pouch for dispensing a biopharmaceutical product via a plurality of output ports to receptacles, such as elementary containers. Such a known pouch firstly comprises an envelope adapted to receive in its interior space the biopharmaceutical product and comprising, united by fixed and sealed zones of attachment, flexible walls, of which two opposite walls connected to one another. by their peripheries. It then comprises at least one port of entry through which the interior space can be filled with the biopharmaceutical product. Finally, it comprises a plurality of output ports for the simultaneous distribution by them of the biopharmaceutical product located in the interior space, to receptacles, such as elementary receptacles. Such an input or output port is associated with a passage of the envelope and mounted on it by means of fixed and sealed connection.

For a biopharmaceutical use such as typically the development, storage or transport of biopharmaceutical product, we generally know flexible bags for single use whose two walls are directly joined to each other by fixed and sealed zones of attachment, for example folding, gluing or welding, and which, when expanded, have a limited volume, for example 20 liters, and remain relatively thin, which justifies that we often call them pockets "Pillow" or "2D" pockets (D meaning dimensions). Flexible single-use flexible pockets are also known which comprise two walls united and secured by means of two welded side gussets, which can be folded extended or unfolded deployed, the volume can then be at least 50 liters, up to 3,000 liters or more. Such 3D pockets are described for example in the document WO00 / 04131 or marketed under the trademark FLEXEL ^® 3D. These 2D or 3D pockets have fixed and sealed securing zones, at least some of which are of the bonding or welding type, and ports interposed at the location of the fastening zones.

For use such as blood collection and treatment or perfusion or parenteral fluid collection, there are known flexible 2D disposable pouches of smaller volume (e.g., typically 500 ml for blood and 50 ml to 3,000 ml for infusion) having ports of entry and at the location of the joining zones by bonding or welding or at least in the terminal portion of the extended pocket, as illustrated for example in the documents US 3,110,308 , US 4,362,158 , and US 3,205,889 . The invention does not relate to these applications.

The document US 2009/0105683 discloses a disposable container for biological products comprising a unitary sheet of biologically compatible flexible material, an access area integrally molded into said sheet, at least one port in said access area to allow fluid biological materials to be introduced into said container, said web being folded along said access area such 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 connecting portion of said upper portion to said lower portion.

The document FR 2528801 describes a sachet for the slow flow of a liquid medium such as an infusion, having at one end at least one tubing at the opposite end a suspension opening, welds closing its lateral edges, the tubings being fixed to a base that is adherent 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.

The document US 4362158 describes a bag for human blood and its fractions, dialysis solutions, infusion solutions ... constituted in such a way that when it is suspended it allows the complete or total evacuation of its contents, thanks to an active means in bellows shape.

The invention relates to a use in which it is a question of filling with a biopharmaceutical product a set of p receptacles, such as similar elementary receptacles of relatively small unit volume, for example of the order of a few milliliters to a few centiliters. under sterile conditions, from the same single-use flexible bag receiving a larger quantity of biopharmaceutical product and having a plurality of n similar output ports, the number p of containers being generally larger, and even much larger, than the number n of output ports. In this case, the filling of all the containers is carried out in several passes, each in which the filling is simultaneous for a number n of containers. In this case, it is generally sufficient that the interior space of the pocket has a volume of between 2 and 20 liters, this value range being given for information only.

For such use, it is important that during the implementation of the pocket, the distribution of the biopharmaceutical product by the n output ports is done simultaneously and identically for the n output ports, particularly with regard to the quality and the quantity of biopharmaceutical product distributed. It is also important that at the end of the process, the pouch can be emptied completely or substantially completely from the biopharmaceutical it contains. These goals are difficult to achieve, if not are, when the pocket has ports of entry and exit arranged at the location of the joining zones by gluing or welding. This is the context and the problem underlying the invention.

For an application and relative to a context other than those of the invention, the document US 3,554,256 describes an intravenous container allowing the addition of drugs or other ingredients (eg vitamin) to the contents of a flexible plastic container for delivery to a patient. This flexible intravenous container has a flexible tubular compression body, each end of which is aseptically sealed. An output connector is provided halfway between the ends to be connected and allows to connect an intravenous tube. The ends of the compression body are adapted to be fixed to a post support so that the compression body can be folded in its middle and its ends easily fixed on the post support, the output connector being disposed at the bottom of the body of contention. At least one additional connector is provided near one of its ends for the addition of drugs or other ingredients. Initially, one end of the tubular compression body is welded and the other end is left open to fill the compression body with liquid intravenously. Then, after this filling, this open end is closed. The container according to the document US 3,554,256 is not intended to be an application and does not relate to a context in which a biopharmaceutical product is to be filled with a plurality of similar unitary units of relatively small unit volume from a single flexible disposable pocket receiving a greater quantity of biopharmaceutical product and having a plurality of n similar output ports, the number p of containers being larger, and even much larger, than the number n of output ports. So, the container according to the document US 3,554,256 on the one hand, does not have an input port of its contents other than one or two ports for adding a drug or other ingredient, and, on the other hand, has only one and only one exit port and not several. Finally, if the container according to the document US 3,554,256 is interested in the question of filling the container with an addition of drugs or other ingredients, he is not interested at all in the problem of the distribution of the contents of the pocket by several ports of exit so that it is done simultaneously and in the same way for the various ports, particularly with regard to the quality and quantity of biopharmaceutical products distributed. He is not more interested in the problem of emptying the entire bag at the end of the process.

There is therefore the unmet need for disposable flexible pouches of the type comprising an envelope adapted to receive in its interior space a biopharmaceutical product and comprising, joined by fixed and sealed securing zones, flexible walls, two walls of which. opposites connected to each other by their peripheries, at least one port of entry through which the inner space can be filled with the biopharmaceutical product, and a plurality of n ports of exit for the distribution of the biopharmaceutical product, such as that during the implementation of the pocket, the distribution of the biopharmaceutical product by the n exit ports is done simultaneously and identically for the different ports, particularly with regard to the quality and quantity of product distributed biopharmaceutical and that at the end of the process, the bag can be emptied totally or substantially completely of the biopharmaceutical product it contains.

The invention aims to meet this need.

For this purpose, according to a first aspect, the subject of the invention is a ladle for dispensing a dose of a biopharmaceutical product in the general liquid or pasty state capable of flow, into a set of receptacles, comprising a envelope adapted to receive in its interior space the biopharmaceutical product and comprising, joined by fixed and sealed zones of attachment, flexible walls, of which two opposite walls connected to each other by their peripheries, at least one port of entry through which the interior space can be filled with the biopharmaceutical product, and a plurality of n output ports which are communicatively associated with n external drain / fill tubes, and through which biopharmaceutical product can be discharged from space interior to a plurality of receptacles communicatively associated with the n output ports to fill them with a dose of biopharmaceutical product, a port being associated é to a passage of the envelope and being mounted on it by means of fixed and sealed connection.

• ▪ les n ports de sortie sont analogues et groupés, en particulier au voisinage les uns des autres, dans une zone de piquage continue et délimitée par les ports de sortie ou leur proximité, située sur une paroi de piquage de l'une des deux parois, distincte des zones de solidarisation, linéairement étendue ou surfaciquement étendue d'aire nettement plus petite que l'aire de la face de la paroi de piquage,
• ▪ la poche comporte une paroi de piquage pourvue d'au moins une ouverture de passage et de montage de port de sortie pour les n ports de sortie, et des moyens de liaison fixe et étanche port/enveloppe solidarisés de façon fixe et étanche à la paroi de piquage autour de la au moins une ouverture de passage et de montage de port de sortie,
• ▪ la poche comporte une zone de pliage des deux parois à l'endroit ou à proximité de laquelle se trouve la zone de piquage, à l'endroit de laquelle les deux parois peuvent être pliées sur elles-mêmes avec la face de la paroi de piquage située à l'extérieur du pli en formant un bord d'extrémité de la poche pliée, à l'endroit ou à proximité duquel est située la zone de piquage et les n ports de sortie.

This pocket is such that:

• The n output ports are similar and grouped, in particular in the vicinity of each other, in a continuous tapping zone delimited by the outlet ports or their proximity, located on a stitching wall of one of the two walls; , distinct from the zones of joining, linearly extended or surfaciquement extended of area much smaller than the area of the face of the wall of stitching,
• ▪ the pocket has a stitching wall provided with at least one opening and outlet port mounting for the n output ports, and fixed and sealed connection means port / envelope firmly fixed and sealed to the stitching wall around the at least one exit and exit port opening,
• ▪ the pocket has a folding zone of the two walls at or near the point where the stitching zone is located, where the two walls can be folded on themselves with the face of the wall of stitching located outside the fold forming an end edge of the folded pocket at or near the location of the stitching area and the n output ports.

Thus, the pocket may be either in an unfolded configuration with both extended walls, or in a folded configuration with the two walls folded on themselves in the folding zone and the face of the stitching wall outside the fold, and in which the pocket can be filled with biopharmaceutical product, with the end edge disposed and maintained as a lower edge, that when the pocket is implemented in the folded configuration, the evacuation of the biopharmaceutical product is done simultaneously and identically by the n output ports and that the biopharmaceutical product is distributed to the plurality of receptacles in communicating association to fill them with a dose of biopharmaceutical product, that this process can be reiterated with several plurality of receptacles, and that once the set of receptacles filled with a dose of biopharmaceutical product, the bag can be emptied totally or substantially completely of biopharmaceutical product.

According to one embodiment, two output ports in the vicinity of each other are spaced apart from each other by a distance chosen so that the flow of the biopharmaceutical product through one of the output ports does not disturb not substantially flow of the biopharmaceutical product through the other output ports.

According to possible embodiments, the surface area of the quill has an area less than 1/5 ^th , more particularly less than 1/10 ^th , more particularly less than 1/20 ^th of the area of the quilting face,

According to one characteristic, the stitching zone is either linearly extended or surface-lengthwise extended along a stitching segment and, in one embodiment, the stitching segment comprises at least one substantially rectilinear section and, in particular, it is substantially straight.

According to one embodiment, the n analog output ports are distributed at least substantially uniformly throughout the quilting zone, and more particularly, are at least substantially regularly spaced from each other.

According to one embodiment, the n analogous output ports are distributed at least substantially uniformly, in particular at least substantially regularly spaced apart from one another, in all of several stitching sub-zones, each stitching sub-zone being continuous. delimited by exit ports or their proximity, and linearly or surface-extended, the plurality of sub-areas of stitching constituting the stitching area being separated by areas without stitching.

According to this embodiment, a stitching sub-zone is either linearly extended or surface-lengthwise extended along a stitching sub-segment, in particular a stitching sub-segment comprising at least one substantially rectilinear section, more especially substantially rectilinear and / or extending at least substantially parallel to the stitching segment.

According to this embodiment, at least some of the stitching sub-segments, in particular all the stitching sub-segments, are located at least substantially parallel to each other or at least substantially in extension of each other.

According to the embodiments, either at an output port and output port aperture is associated with a port of the plurality of n output ports or an output port gateway and output port is common to a plurality of ports. the plurality of n analog output ports is the pocket has a single common port output and output port aperture to the n similar output ports.

According to one embodiment, an output port comprises communicatively associated a draining / filling tube at its proximal end and a securing plate forming part of the fixed and sealed connection means port / envelope, secured, in particular by gluing or welding, in a fixed and watertight manner at the stitching wall around a passage opening and outlet port opening.

According to one embodiment, the emptying / filling tubes are able to be communicatively associated at their distal ends with receptacles for filling them with the biopharmaceutical product, and to be functionally associated with evacuation or withdrawal withdrawal means. / dosing, in particular programmed or ordered.

According to one embodiment, either a connection plate is associated with an output port or a connection plate is common to several output ports, or the pocket has a single joint plate common to the n output ports.

According to one embodiment, the pocket has as many fastening plates as stitching sub-zones, each fastening plate being associated with a stitching sub-zone.

In one embodiment, a fastening plate has an internal face shaped to facilitate the emptying, in particular the complete emptying, of the biopharmaceutical product.

According to one embodiment, the stitching zone and / or the folding zone is located at or near the central zone of the face of the stitching wall and / or a central axis of the face of the wall. stitching between the opposite periphery sections of the face of the stitching wall.

In one embodiment, no port is located on the face opposite to the face of the stitching wall and / or in the securing zones.

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

According to one embodiment, an input port comprises communicatively associated a filling / feeding tube at its proximal end, adapted to be associated in a communicating manner at its distal end to a biopharmaceutical product supply, with in particular interposition of a filter, and able to be associated functionally with means of stopping supply or feeding / dosing, in particular programmed or controlled.

In particular, the bag comprises a plurality of input ports, each communicatively associated with a first section of filling / feeding tube at its proximal end, said plurality of first filling / feeding tube sections being associated with each other. communicating manner at their distal ends to the proximal end of a second common section of filling / feeding tube adapted to be associated in a communicating manner at its distal end to the supply of biopharmaceutical product, with in particular the interposition of a common filter, the supply stop or feed / dosing means being associated with the second common section of filling / feeding tube.

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

According to one embodiment, the areas of the face of the stitching wall and the opposite face spaced apart from the folding zone and the stitching zone form suspension zones of the pocket in its folded configuration, including suspension members, such as holes or projections.

In one embodiment, the bag comprises means able to keep the two opposite walls folded on themselves when the bag is in the folded configuration, including holding members complementary to each other.

According to one characteristic, the bag is in an unfolded configuration in which the two opposite walls are extended.

According to another characteristic, the bag is in a folded configuration in which the two opposite walls are folded on themselves in the fold zone with the face of the stitching wall located outside the fold, the pocket in the configuration. folded having, in the fold zone, an end edge at or near the location of the stitching area and the n output ports.

According to a development, the pocket comprises means capable of maintaining a permanent communication between the two inner subspaces located on either side of the folding zone.

According to one characteristic, the bag is a pocket of the 2D type, essentially comprising two flexible walls of the same shape, joined by zones of attachment to their peripheries.

According to one characteristic, the interior space of the pocket has a volume of between 2 liters and 20 liters.

In one embodiment, the pouch is sterilized.

• ▪ une poche de distribution d'une dose d'un produit biopharmaceutique ayant une configuration pliée, en particulier une poche à l'état empli de produit biopharmaceutique,
• ▪ des moyens de maintien de ladite poche propres à ce que le bord d'extrémité situé à l'endroit ou à proximité de la zone de pliage soit le bord inférieur de la poche, l'espace intérieur étant placé le plus au-dessus,
• ▪ des moyens d'association de façon communicante de l'extrémité distale des tubes de vidange/emplissage à des réceptacles pour leur emplissage avec le produit biopharmaceutique se trouvant dans l'espace intérieur de la poche,
• ▪ des moyens d'arrêt d'évacuation ou de soutirage/dosage, en particulier programmés ou commandés, associés fonctionnellement aux tubes de vidange/emplissage.

According to a second aspect, the subject of the invention is a set of dispensing a dose of a liquid or pasty general flowable biopharmaceutical product, in a set of receptacles, comprising:

• ▪ a pocket for dispensing a dose of a biopharmaceutical product having a folded configuration, in particular a pocket filled with a biopharmaceutical product,
• ▪ Means for maintaining said pocket adapted so that the end edge located at or near the folding zone is the lower edge of the pocket, the interior space being placed at the top,
• ▪ means for communicatively associating the distal end of the emptying / filling tubes with receptacles for filling them with the biopharmaceutical product in the inside of the bag,
• ▪ means for stopping discharge or withdrawal / dosing, in particular programmed or controlled, functionally associated with the drain / fill tubes.

In one embodiment, wherein the bag is such that an inlet port comprises communicatively associated with a filling / feeding tube at its proximal end, the dispensing assembly also comprises connecting means in a communicating manner of the distal end of the filling / feeding tube to the biopharmaceutical product supply, and supply or feed / dosing stop means, in particular programmed or controlled, functionally associated with the filling / feeding tube for filling the inner space of the pocket with the biopharmaceutical product from the biopharmaceutical product feed.

According to one embodiment, the means for stopping evacuation or withdrawal / metering functionally associated with the emptying / filling tubes comprise a pump, such as a peristaltic pump or a pump known as "RDP" (for Rolling Diaphragm Pump) or a similar pump, structurally associated with each drain / filling tube set for the distribution of successive doses of biopharmaceutical product, and / or the power supply or feed / dosing means associated in a functional manner. to the filling / feeding tube comprise a pump structurally associated with the filling / feeding tube.

• ▪ des moyens de détection du dépassement d'une quantité minimale et d'une quantité maximale de produit biopharmaceutique se trouvant dans l'espace intérieur de la poche,
• ▪ et des moyens de commande des moyens d'arrêt d'évacuation ou de soutirage/dosage associés aux tubes de vidange/emplissage et des moyens d'arrêt d'alimentation ou d'alimentation/dosage associés au tube d'emplissage/alimentation, responsifs auxdits moyens de détection du dépassement, de sorte que lorsque la quantité de produit biopharmaceutique se trouvant dans l'espace intérieur de la poche atteint la quantité minimale, les moyens de commande commandent le fonctionnement des moyens d'arrêt d'alimentation ou d'alimentation/dosage associés au tube d'emplissage/alimentation pour emplir l'espace intérieur de la poche avec le produit biopharmaceutique provenant de l'alimentation en produit biopharmaceutique et que lorsque la quantité de produit biopharmaceutique se trouvant dans l'espace intérieur de la poche atteint la quantité maximale, les moyens de commande commandent le fonctionnement des moyens d'arrêt d'alimentation ou d'alimentation/dosage associés au tube d'emplissage/alimentation pour cesser d'emplir l'espace intérieur de la poche avec le produit biopharmaceutique provenant de l'alimentation en produit biopharmaceutique.

According to one embodiment, the distribution assembly also comprises:

• Means for detecting the exceeding of a minimum quantity and a maximum quantity of biopharmaceutical product located in the interior space of the pocket,
• And means for controlling the means for stopping the evacuation or withdrawal / metering associated with the emptying / filling tubes and means for stopping supply or feeding / dosing associated with the filling / feeding tube, responsive to said overshoot detection means, such that when the amount of biopharmaceutical product in the inner space of the bag reaches the minimum amount, the control means controls the operation of the feed stop means or feeding / dosing associated with the filling / feeding tube to fill the inner space of the pocket with the biopharmaceutical product from the biopharmaceutical product feed and when the amount of biopharmaceutical product in the inner space of the bag reaches the maximum amount, the control means controls the operating the feed stop or feed / dosing means associated with the filling / feeding tube to stop filling the inner space of the bag with the biopharmaceutical product from the biopharmaceutical product feed.

• ▪ des moyens d'amenée d'une pluralité, en particulier de n, réceptacles ne contenant pas encore ladite dose de produit biopharmaceutique,
• ▪ des moyens d'évacuation d'une pluralité, en particulier de n, réceptacles contenant ladite dose de produit biopharmaceutique.

According to one embodiment, the distribution assembly also comprises:

• Feed means of a plurality, in particular of n receptacles not yet containing said dose of biopharmaceutical product,
• Means of evacuation of a plurality, in particular of n receptacles containing said dose of biopharmaceutical product.

In one embodiment, the receptacles are located within an aseptic chamber and the biopharmaceutical product supply is located outside the aseptic chamber, the bag being located either indoors or outdoors of the aseptic chamber, the wall of the aseptic chamber being traversed respectively by the drain / filling tubes or by a filling / feeding tube.

• ▪ l'on dispose d'une poche flexible ayant une configuration non pliée tel que décrite précédemment,
• ▪ l'on dispose du produit biopharmaceutique,
• ▪ l'on dispose de p réceptacles ne contenant pas encore ladite dose de produit biopharmaceutique,
• ▪ en premier lieu, l'on plie la poche dans sa zone de pliage de sorte que les deux parois opposées sont pliées sur elles-mêmes avec la face de la paroi de piquage située à l'extérieur du pli en formant un bord d'extrémité de la poche pliée, à l'endroit ou à proximité duquel est située la zone de piquage et les n ports de sortie et ainsi l'on amène la poche dans sa configuration pliée tel que décrite précédemment, en deuxième lieu, l'on emplit l'espace intérieur de la poche avec le produit biopharmaceutique, via au moins un port d'entrée, en troisième lieu, l'on associe de façon communicante les n ports de sortie à une première pluralité, en particulier de n, réceptacles ne contenant pas encore ladite dose de produit biopharmaceutique, et en quatrième lieu, l'on dispose et l'on maintien le bord d'extrémité de sorte qu'il soit et reste le bord supérieur de la poche,
• ▪ puis, l'on assure l'évacuation du produit biopharmaceutique par les n ports de sortie, simultanément, et l'on distribue une même dose de produit biopharmaceutique dans ladite première pluralité de réceptacles, de sorte à obtenir une première pluralité de réceptacles contenant ladite dose de produit biopharmaceutique,
• ▪ puis, alors que l'on empêche l'évacuation du produit biopharmaceutique par les n ports de sortie, l'on évacue ladite première pluralité de réceptacles contenant ladite dose de produit biopharmaceutique, et l'on amène une deuxième pluralité, en particulier de n, réceptacles ne contenant pas encore ladite dose de produit biopharmaceutique, et on réitère le processus avec cette deuxième pluralité de réceptacles, et ainsi de suite jusqu'à ce que l'on ait empli les p réceptacles.

According to a third aspect, the subject of the invention is a dispensing method for the implementation of a pocket for dispensing a dose of a biopharmaceutical product as described, with a view to dispensing the same dose of biopharmaceutical product by the plurality of n output ports in p receptacles, the number p of receptacles being larger, and even much larger, than the number n of output ports, wherein:

• A flexible pouch having an unfolded configuration as described above,
• ▪ the biopharmaceutical product is available,
• ▪ there are receptacles not yet containing the said dose of biopharmaceutical product,
• In the first place, the pocket is folded in its folding zone so that the two opposite walls are folded on themselves with the face of the stitching wall located outside the fold forming an edge of end of the folded pocket, at the place where the stitching zone and the n exit ports are situated, and thus the pocket is brought into its folded configuration as described above, and secondly, fills the inner space of the pocket with the biopharmaceutical product, via at least one input port; thirdly, the n output ports are communicatively associated with a first plurality, in particular n, containers not yet containing said dose of biopharmaceutical product, and fourthly, the end edge is disposed and maintained so that it is and remains the top edge of the pocket,
• ▪ then, the evacuation of the biopharmaceutical product by the n exit ports is carried out simultaneously, and the same dose of biopharmaceutical product is distributed in the first plurality of receptacles, so as to obtain a first plurality of receptacles containing said dose of biopharmaceutical product,
• ▪ then, while preventing the evacuation of the biopharmaceutical product by the n exit ports, evacuating said first plurality of receptacles containing said dose of biopharmaceutical product, and bringing a second plurality, in particular of n, receptacles not yet containing said dose of biopharmaceutical product, and the process is repeated with this second plurality of receptacles, and so on until the receptacles have been filled.

According to the embodiments, firstly the bag is 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 pocket is folded.

According to one embodiment, there are furthermore means for holding the pocket and in which they are implemented so that the end edge of the pocket located at or near the zone of folding is the lower edge of the pocket, the interior space being placed above.

• ▪ d'une part, l'on amène par les moyens d'amenée, une pluralité, en particulier de n, réceptacles ne contenant pas encore ladite dose de produit biopharmaceutique et l'on associe de façon communicante l'extrémité distale des tubes de vidange/emplissage à ladite pluralité de réceptacles,
• ▪ d'autre part, l'on évacue par les moyens d'évacuation, une pluralité, en particulier de n, réceptacles contenant ladite dose de produit biopharmaceutique.

According to one embodiment:

• On the one hand, a plurality, in particular n receptacles not containing the said dose of biopharmaceutical product, is brought by the supply means and the distal end of the draining / filling said plurality of receptacles,
• ▪ on the other hand, a plurality, in particular of n receptacles containing said dose of biopharmaceutical product, is evacuated by the evacuation means.

• ▪ avec les moyens de détection, l'on détecte le dépassement d'une quantité minimale et d'une quantité maximale de produit biopharmaceutique se trouvant dans l'espace intérieur de la poche,
• ▪ et, en fonction de la détection effectuée et avec les moyens de commande, l'on commande les moyens d'arrêt d'évacuation ou de soutirage/dosage associés aux tubes de vidange/emplissage et des moyens d'arrêt d'alimentation ou d'alimentation/dosage associés au tube d'emplissage/alimentation, de sorte que lorsque la quantité de produit biopharmaceutique se trouvant dans l'espace intérieur de la poche atteint la quantité minimale, l'on commande le fonctionnement des moyens d'arrêt d'alimentation ou d'alimentation/dosage associés au tube d'emplissage/alimentation pour emplir l'espace intérieur de la poche avec le produit biopharmaceutique provenant de l'alimentation en produit biopharmaceutique et que lorsque la quantité de produit biopharmaceutique se trouvant dans l'espace intérieur de la poche atteint la quantité maximale, l'on commande les moyens d'arrêt d'alimentation ou d'alimentation/dosage associés au tube d'emplissage/alimentation pour cesser d'emplir l'espace intérieur de la poche avec le produit biopharmaceutique provenant de l'alimentation en produit biopharmaceutique.

According to one embodiment:

• With the detection means, it is detected that a minimum quantity and a maximum quantity of biopharmaceutical product in the internal space of the pocket have been exceeded,
• And, depending on the detection carried out and with the control means, the evacuation or withdrawal / dosing stop means associated with the emptying / filling tubes and the means for stopping feeding or feeding / dosing associated with the filling / feeding tube, so that when the quantity of biopharmaceutical product in the inner space of the bag reaches the minimum quantity, the operation of the stop means is controlled. feeding or feeding / dosing associated with the filling / feeding tube to fill the inner space of the bag with the biopharmaceutical product from the biopharmaceutical product feed and that when the quantity of biopharmaceutical product in the biopharmaceutical product internal space of the pocket reaches the maximum quantity, it controls the means of stopping supply or feeding / dosing associated with the filling / feeding tube to stop filling the space inside the pouch with the biopharmaceutical product from the biopharmaceutical product feed.

• ▪ l'on dispose de film en matière plastique apte à être découpé et solidarisé sur lui-même et à former des parois flexibles de poche,
• ▪ l'on dispose d'au moins un port d'entrée et d'une pluralité de n ports de sortie,
• ▪ l'on dispose de moyens de découpe de film et de moyens de solidarisation,
• ▪ l'on découpe le film à la forme souhaitée des parois de la poche, en particulier les deux parois opposées,
• ▪ l'on découpe dans une paroi de piquage au moins une ouverture de passage et de montage de port de sortie pour les n ports de sortie,
• ▪ et l'on solidarise de façon fixe et étanche les parois de la poche et les ports de sortie à la paroi de piquage autour de la au moins une ouverture de passage et de montage de port de sortie.

According to a fourth aspect, the subject of the invention is a method for producing a dispensing bag, in which:

• ▪ there is plastic film capable of being cut and secured to itself and to form flexible pocket walls,
• ▪ there is at least one input port and a plurality of n output ports,
• ▪ film cutting means and fastening means are available,
• ▪ the film is cut to the desired shape of the walls of the pocket, in particular the two opposite walls,
• ▪ at least one exit and exit port opening aperture is cut in a stitching wall for the n output ports,
• ▪ and securely and securely affixes the walls of the pocket and the output ports to the stitching wall around the at least one opening port and exit port mounting.

According to one embodiment, there is communicatively associated a drain / filling tube at its proximal end and a securing plate and the securing plate is secured, in particular by gluing or welding, in a fixed and watertight manner. stitching wall around an opening port and outlet port mounting.

According to one embodiment, at an input port, a filling / supply tube is communicatively associated with its proximal end, in particular, the bag comprising a plurality of input ports, one associates with each a first section of filling / feeding tube at its proximal end, and communicatively associating said plurality of first filling / feeding tube sections at their distal ends with the proximal end of a second common section of filling / feeding tube.

• la figure 1 est une vue en élévation d'une poche de distribution flexible 2D à usage unique selon l'invention dans la configuration non pliée et à l'état vide de produit biopharmaceutique, cette poche comportant ici - et à titre purement exemplatif - six ports de sortie analogues de produit biopharmaceutique avec des platines, des tubes de vidange/emplissage associés de façon communicante à leurs extrémités proximales aux ports de sortie et représentés de façon partielle, et des moyens d'arrêt d'évacuation ou de soutirage/dosage représentés ici de façon purement symbolique, deux ports d'entrée, ici sans tube d'emplissage/alimentation, situés à proximité de la zone de piquage des ports de sortie surfaciquement linéairement étendue, en étant plus près de la périphérie proche de la paroi de piquage que les ports de sortie, quatre ports d'entrée/sortie de gaz, deux trous de suspension, la poche étant vue du côté de la face de piquage,
• la figure 2 est une vue en élévation analogue à la figure 1, la poche étant vue du côté de la face opposée à la face de piquage,
• la figure 3 est une vue de dessus de la poche de la figure 1,
• la figure 4 est une vue de côté de la poche des figures 1 et 2,
• la figure 5 est une vue en élévation illustrant une partie d'un ensemble de distribution selon l'invention, comprenant la poche des figures 1 à 4 dans la configuration pliée avec la face de piquage située à l'extérieur du pli, et suspendue, tel que la poche comporte un bord d'extrémité dans la zone de piquage et les ports de sortie analogues, la poche étant vue d'un premier côté, la poche étant en situation de distribuer le produit biopharmaceutique à un ensemble de p réceptacles, ici d'emplir un ensemble de p récipients élémentaires, les tubes de vidange/emplissage étant associés de façon communicante à leurs extrémités distales à ces récipients et étant associés fonctionnellement aux moyens d'arrêt d'évacuation ou de soutirage/dosage représentés symboliquement, comme précédemment, la figure montrant également des moyens de maintien de la poche propres à ce que le bord d'extrémité situé à l'endroit ou à proximité de la zone de pliage soit le bord inférieur de la poche et que l'espace intérieur de la poche est placé le plus au-dessus,
• la figure 6 est une vue analogue à la figure 5, la poche étant vue du second côté opposé au premier côté,
• la figure 7 est une vue de côté de l'ensemble de distribution et de la poche des figures 5 et 6, alors que la poche est à l'état empli de produit biopharmaceutique,
• les figures 8A et 8B sont deux vues schématiques simplifiées d'une poche 2D dans la configuration non pliée et à l'état vide de produit biopharmaceutique, illustrant différentes possibilités de réalisation en ce qui concerne les ports de sortie analogues de produit biopharmaceutique et les ports d'entrée, à savoir, en ce qui concerne la figure 8A, douze ports de sortie analogues en deux sous-zones surfaciquement linéairement étendues, disposées à proximité l'une de l'autre de façon parallèle et un port d'entrée écarté de la zone de piquage mais situé sur la face de piquage et, en ce qui concerne la figure 8B, six ports de sortie analogues en deux sous-zones surfaciquement étendues et un port d'entrée situé dans la zone de piquage entre les deux sous-zones de piquage,
• la figure 9 est une vue en coupe à plus grande échelle illustrant un port de sortie avec un tronçon de tube et à son extrémité proximale une platine de solidarisation faisant partie des moyens de liaison fixe et étanche port/enveloppe, solidarisée de façon fixe et étanche à la paroi de piquage autour d'une ouverture de passage et de montage de port de sortie,
• la figure 10 est un schéma illustrant une partie d'un ensemble de distribution selon l'invention incluant une poche de distribution dans la configuration pliée et l'état empli, comme dans la figure 7, les moyens de maintien et les réceptacles (ou récipients) n'étant pas ici représentés, les moyens d'arrêt d'évacuation ou de soutirage/dosage, associés fonctionnellement aux tubes de vidange/emplissage étant représentés de façon symbolique, la poche ayant deux ports d'entrée avec, associé de façon communicante, un tube d'emplissage/alimentation à son extrémité proximale, et des moyens d'association de façon communicante de l'extrémité distale du tube d'emplissage/alimentation à une alimentation en produit biopharmaceutique, et des moyens d'arrêt d'alimentation ou d'alimentation/dosage, associés fonctionnellement au tube d'emplissage/alimentation représentés de façon symbolique.

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

• the figure 1 is an elevational view of a 2D single-use flexible dispensing bag according to the invention in the unfolded and empty configuration of a biopharmaceutical product, this pouch comprising here - and purely exemplary - six output ports biopharmaceutical product analogs with platinums, draining / filling tubes communicatively associated at their proximal ends to the outlet ports and partially depicted, and discharge stop or withdrawal / dosing means shown here in such a manner as to purely symbolic, two input ports, here without filling tube / power supply, located near the area of quilting output ports surfaciquement linearly extended, being closer to the periphery close to the quilting wall that the ports four gas inlet / outlet ports, two suspension holes, the pocket being viewed from the side of the quilting face,
• the figure 2 is an elevation view similar to the figure 1 the pocket being viewed from the opposite side of the stitching face,
• the figure 3 is a top view of the pocket of the figure 1 ,
• the figure 4 is a side view of the pocket of Figures 1 and 2 ,
• the figure 5 is an elevational view illustrating a portion of a dispensing assembly according to the invention, comprising the pocket of Figures 1 to 4 in the folded configuration with the stitching face located outside the fold, and suspended, such that the pocket has an end edge in the stitching area and the like output ports, the pocket being viewed from a first side, the bag being in a position to dispense the biopharmaceutical product to a set of p containers, here to fill a set of p elementary containers, the emptying / filling tubes being associated communicatively at their distal ends to these containers and being functionally associated with the means for stopping evacuation or withdrawal / metering represented symbolically, as above, the figure also showing means for maintaining the pocket, such that the end edge located at or near the the folding zone is the lower edge of the pocket and the inside space of the pocket is placed at the top,
• the figure 6 is a view similar to the figure 5 the pocket being viewed from the second side opposite to the first side,
• the figure 7 is a side view of the distribution set and the pocket of Figures 5 and 6 , while the bag is in the filled state of biopharmaceutical product,
• the Figures 8A and 8B are two simplified schematic views of a 2D pocket in the unfolded, empty configuration of a biopharmaceutical product, illustrating different possibilities of realization with respect to biopharmaceutical analog output ports and ports of entry, know, as far as the figure 8A , twelve analogous output ports in two sub-areas surfaciquement linearly extended, disposed in close proximity to each other and an inlet port spaced from the quilting area but located on the quilting face and, in regarding the Figure 8B , six analogous output ports in two sub-areas with a large surface area and an input port located in the stitching zone between the two stitching sub-zones,
• the figure 9 is a sectional view on a larger scale illustrating an outlet port with a tube section and at its proximal end a fixing plate forming part of the fixed and sealed connection means port / envelope, fixedly secured and sealed to the wall stitching around an opening port and outlet port mounting,
• the figure 10 is a diagram illustrating a portion of a dispensing assembly according to the invention including a dispensing bag in the folded configuration and the filled state, as in the figure 7 , the holding means and the receptacles (or containers) not being shown here, the discharge stop or withdrawal / dosing means, functionally associated with the emptying / filling tubes being symbolically represented, the bag having two input ports with communicatively associated filling / feeding tube at its proximal end, and communicatively connecting means from the distal end of the filling / feeding tube to a feed of product biopharmaceutical, and feed stop or feed / dosing means operatively associated with the fill / feed tube symbolically represented.

We now refer more specifically to Figures 1 to 7 and 10 which represent a dispensing pocket, 2D, flexible as a whole, disposable, specially intended for use biopharmaceutical for dispensing a biopharmaceutical product into a set of receptacles, such as here a set of elementary receptacles 2. Such a pouch 1 is intended to be part of it being incorporated into a dispensing assembly.

The biopharmaceutical product is a product in the general state liquid or pasty, that is to say, able to flow, resulting from biotechnology or having a pharmaceutical purpose.

The pocket 1 comprises an envelope 3 delimiting an interior space 3a able to receive the biopharmaceutical product. This envelope 3 comprises, joined by fixed and sealed zones of attachment 4, two opposite flexible walls 5 and 6, one of which - the wall 5 - is called the stitching wall, the two walls 5 and 6, facing each other. one of the other, being connected to each other by their peripheries 7.

The two walls 5 and 6 are here of the same general shape and of similar size, such that having an outline at least substantially square or rectangular. Such a wall 5 or 6 thus has two pairs of opposite periphery sections, namely the pair of sections 7a extending in their entirety substantially in the same first direction, here forming the short sides (arranged horizontally in the figures), and the pair of sections 7b extending in their entirety substantially in the same second direction orthogonal to the first direction, here forming the long sides (arranged vertically in the figures). The first direction of the sections 7a defines a parallel axis AA which is central on the pocket 1 and which, during the implementation of the pocket 1, is placed horizontally or substantially horizontally, and which is also an axis of a zone of folding 8 of the walls 5 and 6 and the pocket 1. The sections 7b here define a principal axis BB of symmetry of the pocket 1 which, during the implementation of the pocket 1, is placed vertically or substantially vertically, and which is also a pocket holding axis 1 for its implementation.

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

The realization of the two walls 5 and 6 which has just been described is only exemplary and not limiting. It is the same for the realization of the envelope 2 in the form of a 2D pocket.

The inner space 3a of the pocket 1 can have a volume of between 2 liters and 20 liters. Such a volume is well adapted, generally, to a use in which it is necessary to fill the biopharmaceutical product the plurality of similar elementary receptacles 2, each relatively small unit volume, for example of the order of a few milliliters to a few cl

Such elementary receptacles 2 may be chosen from the group comprising vials, syringes, vials and bottles, pouches or bag systems for single use or not. Their unit volume is a fraction of the volume of the interior space 3a of the pocket 1.

The flexible walls 5 and 6 of the bag 1 are typically made from monolayer or multilayer plastic film, in particular comprising PE, PP, EVOH, etc. They are secured in the bonding zones 4 by bonding. , or possibly gluing or in any other way. These achievements are only exemplary and in no way limiting. Thus, it is possible that on such or such section 7a, 7b of periphery 7, the walls 5 and 6 are connected to one another by a fold.

The pocket 1 also comprises at least one input port 9 and a plurality of n analog output ports 10, capable of emptying the biopharmaceutical product received in the interior space 3a, so as to distribute the biopharmaceutical product from the plurality of output ports 10, especially in the application more specifically targeted, to fill the elementary receptacles 2 whose number p may be equal to the number n of the output ports 10, each elementary container 2 can thus be associated with a port output 10, because the output ports 10 and the containers 2 are put into communication.

According to one embodiment, an appropriate number of elementary containers 2 are filled with a single pocket contents 1. In this case, it can be envisaged to close the entry port 9 once the interior space 3a of the pocket has been filled. the necessary amount of biopharmaceutical product. According to another embodiment, the desired number of elementary containers 2 are filled with several successive contents of the same pocket 1. In this case, it is intended to adapt the distribution assembly as will be described later in reference to the figure 10 .

In the embodiments more particularly targeted by the figures, the pocket 1 may comprise a plurality of at least four output ports 10, more particularly at least eight output ports 10, and more particularly, at least twelve ports. 10. On the figure 10 , there are provided ten output ports 10. These digital data are only exemplary and not limiting. They mean that the bag has not only a single output port but a greater or lesser plurality, depending on the application, in particular the number of elementary containers 2 to be filled, at least to be filled at each pass of the filling process. .

In this case, the pocket 1 includes other ports suitable to perform a function other than the emptying and the distribution of the biopharmaceutical product.

In the achievements of Figures 1 to 7 , the pocket 1 further comprises one or more ports 11 of inlet and / or gas outlet.

In the realization of Figures 1 to 7 and 10 , the pocket 1 is constituted, with respect to the output ports 10, of the plurality of n analog output ports 10, except the ports 11 input and / or gas outlet.

A port 9, 10, 11 is associated with an appropriate passage of the envelope 3 and mounted on it by means of fixed and sealed connection.

The ports 10 of the plurality of n analog output ports 10 are grouped in a tapping zone 12. "Grouped" means that the output ports 10, located in the vicinity of each other, are together in the quilting zone 12. Thus, the quilting zone 12 sets the limit in which the output ports 10 are located, this limit being adjacent to the output ports 10 or located at a low, and in particular very low, distance from the ports of Exit 10. Here is meant by "adjacent", which is immediately adjacent or adjoining. Here, the term "located at a short distance" means a distance of the order of one centimeter for walls 5 and 6 having dimensions of the order of 10 cm to 60 cm, as indicated above. It is understood that these numerical data are only exemplary and in no way limiting. They express that the quilting zone 12 does not extend beyond a small distance from the output ports 10.

In combination with the previous arrangement, it is provided that two output ports 10 in the vicinity of each other are however spaced from each other by a distance suitable for the flow of the biopharmaceutical product. through one of the ports of exit 10 does not disturb substantially, or even not at all, the flow of the biopharmaceutical product through the other outlet ports 10. Thus, the evacuation of the biopharmaceutical product through the different ports 10, and the filling of the containers 2, can be done simultaneously and identical.

The quilting zone 12 is continuous and delimited by the output ports 10 or their proximity. It should be understood that the quilting zone 12 sets the limit in which the output ports 10 are located, this limit being adjacent to the output ports 10 or located at low, and in particular very low, distance from the output ports 10. "Adjacent" means immediately adjacent or adjoining. Here, the term "located at a short distance" means a distance of the order of one centimeter for walls 5 and 6 having dimensions of the order of 10 cm to 60 cm, as indicated above. It is understood that these numerical data are only exemplary and in no way limiting. They express that the quilting zone 12 does not extend beyond a small distance from the output ports 10.

The stitching zone 12, thus defined, is not necessarily identified as such on the pocket 1.

The quilting zone 12 is located on the quilting wall 5 being distinct from the fastening zones 4. And therefore the output ports 10 are also located on the quilting wall 5 and no output port 10 is located in the quilting areas 5. In addition, no outlet port 10 is located on the face 4 opposite to the stitching face 5. As a result, the stitching wall 5 is provided with at least one opening for passage and mounting 14 of output port 10, for the n analog output ports 10.

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

The quilting zone 12 is linearly extended or surface-surfaced with an area much smaller than the area of the quilting face 5. By "linearly extended" it is meant that the quilting zone is essentially a line or a line , possibly having a certain thickness, which extends along a stitching segment. The term "surface-extended" means that the quilting zone is essentially a surface, as opposed to a line or a line, even having a certain thickness. In one embodiment, the quilting zone 12 is surfacically extended linearly. "Surfacically extended linearly" means that the quilting zone is a surface but that it extends substantially along a line or a line, which itself extends along a segment of stitching 13. In the achievements represented on the Figures 1 to 7 such a stitching segment 13 is substantially rectilinear. In other embodiments, the stitching segment 13 comprises at least one substantially rectilinear section.

By the fact that the area of the quilting zone 12 is surface-expanded with a "much smaller" area than the area of the quilting face 5, the fact that the area of the quilting zone 12 is less than ^1/5 of the area of the stitching face 5, more preferably is less than ^1/10, more particularly is less than ^1/20.

A port 10 is associated with and mounted on the casing 3 by fixed and sealed connection means 15 fixedly and sealingly secured to the stitching wall 5 around the at least one port opening and mounting opening 14. output 10.

We refer more specifically to the figure 9 which shows that an output port 10 comprises, communicatively associated, a tube 16 for emptying / filling at its proximal end 16a towards the casing 3, a fastening plate 17, which is part of the fixed and sealed connection means port / envelope 15. The draining / filling tube 16 has a distal end 16b. The tube 16 is called "emptying / filling" for the reason that it ensures both the emptying of the interior space 3a and the filling of the containers 2. It is in the embodiment considered a flexible tube so that, on the one hand, are contour can be made more or less tormented depending on the requirements of the geometry of the space where it is located (see figure 10 ) and that, on the other hand, it can be crushed locally as needed to cooperate with a stop member such as a clamp (for example a Halkey-Roberts clamp, well known to those skilled in the art ), or a drive-dosing or withdrawal / dosing device, such as a pump, such as a peristaltic pump or a pump known under the RDP anagram for "Rolling Diaphragm Pump" or another functionally similar pump. This organ or device is designated as a whole by the reference 21 and represented in a purely symbolic manner. The fastening plate 17 is fixedly and sealingly secured to the stitching wall 5 around a passage opening and mounting opening 14 of the output port 10. For this purpose, the fastening plate 17 is extended on the wall stitching 5 around a passage opening and mounting 14 of the output port 10 and secured to the stitching wall 5 in a fixed and sealed manner by gluing or welding or by any other means ensuring in combination mechanical strength and sealing, without creating an obstacle to the flow of the biopharmaceutical product. According to the embodiments, the fastening plate 17 is secured by its external face to the internal face of the stitching wall 5 ( figure 9 ), the inner face 17a of the securing plate 17 is then free or, conversely, the fastening plate 17 is secured by its inner face 17a to the outer face of the stitching wall 5. The words "internal" and "external" Refers to what is, respectively, in or turned to the interior space 3a, and out or turned to the opposite side of the interior space 3a. The embodiment more particularly described and shown with regard to the tube 16 of emptying / filling is only indicative and not limiting. The different tubes have the same length or not, the objective being that they deliver the same dose of biopharmaceutical product. Depending on the needs, the tubes 16 of emptying / filling are of a greater or lesser length or more or less small. If the realization by means of flexible tubes is advantageous, in particular for the satisfaction of the objectives of conformation and crushing pinching, it is not exclusive of others, the means associated with the tubes 16 being adapted accordingly, which is to the scope of the skilled person.

The fastening plate 17 has an opening 17b, through, in communication, on the internal side, with the internal space 3a and, on the opposite side, external, with the passage formed by the tube section 16. The fastening plate 17a thus a general annular or pseudo-annular or multi-annular form, if it comprises several openings 17b.

The foregoing embodiments of the fixed and sealed connection means 15 are only exemplary and in no way limiting.

According to the embodiments and the needs, an input port 9 has no associated tube ( Figures 1 to 6,8A, 8B ) or, like an output port 10, and as illustrated by the figure 10 , is communicatively associated with a filling / feeding tube at its proximal end 25a. The tube 25 is termed "filling / feeding" for the reason that it ensures both the filling of the interior space 3a and the supply of biopharmaceutical product. This filling / feeding tube is adapted to be communicatively associated at its distal end 25b with a biopharmaceutical product feed 26, such as a large capacity tank. There may be provided a filter 27 interposed on the filling / feeding tube. It may also be provided that the filling / feeding tube 25 is adapted to be functionally associated, and is functionally associated with, means for stopping feed or supply / dosing 28. These means 28 are represented in such a way that purely symbolic on the figure 10 . Depending on the embodiments, it may be a collet adapted to close the filling / feeding tube by crushing / clamping or a pump, such as, in particular, a peristaltic pump or an RDP pump or another functionally similar pump. Such means 28 may in particular be programmed or controlled.

More specifically, in the realization of the figure 10 where the bag 1 comprises two input ports 9, each of them is communicatively associated with a first section 29a of filling / feeding tube 25 at its proximal end 25a. The first two feed / supply tube sections 29a are communicatively associated at their distal ends 29a with the proximal end 30a of a second common feed / supply pipe section 30 adapted to be associated communicating at its distal end 25b to the supply 26. In this case, the filter 27 and the supply or supply / dosing stop means 28 are, in the example shown in the figure, associated with the second section common 30.

This embodiment of the input port 9 is particularly well suited according to the embodiment already mentioned in which the desired number of elementary containers 2 are filled with several successive contents of the same pocket 1, which is recharged as a biopharmaceutical product at each as necessary when it has been emptied for distribution to receptacles 2.

What has been described and indicated as to the structure of the draining / filling tubes 16 may be transposed to the filling / feeding tube (s).

The pocket 1 also comprises the folding zone 8 of the two opposite walls 5 and 6.

The term "folding zone" means an area where the walls of the pocket 1 can be deformed so as to be folded back on themselves, in order to have two thicknesses of pairs of walls 5 and 6, each thickness comprising both walls 5 and 6. It is understood that the edge 18 of the fold of the folding zone 8 may be more or less marked, ranging from a fairly straight straight line to a simple curvature or curvature, where appropriate with a bulge such as illustrated by the figures 7 and 10 . This folding zone 8 is however very localized and a smaller area than the area of the stitching face 5. The term "smaller", less than of the order of 1/4 ^th.

This embodiment of the folding zone 12 is only exemplary and in no way limiting.

The quilting zone 12 is located at or near the folding zone 8. This means that the two zones 8 and 12 overlap, at least substantially, or that the two zones 8 and 12 are adjacent or located at low, and in particular very low, distance from one another. Here we mean "adjacent", which is immediately adjacent or adjoining. Here, the term "located at a short distance" means a distance of the order of one centimeter for walls 5 and 6 having dimensions of the order of 10 cm to 60 cm, as indicated above. It is understood that these numerical data are only exemplary and in no way limiting. They express that the quilting zone 12 is merged with the folding zone 12, although the two zones do not have the same area, or that the two zones are very close to one another.

At the location of the folding zone 8, the two opposite walls 5 and 6 can be folded on themselves, in the sense that has been explained above, with the stitching face 5 located outside the fold that forms the folding zone 12. The edge 18 of the fold of the folding zone 12 forms an end edge 18 of the pocket 1 in its folded configuration ( Figures 5 to 7 ).

The stitching zone 12 and the n analog output ports 10 are located at or near the end edge 18. This means that the stitching zone 12 and the exit ports 10 and the edge of the end 18 are superimposed, at least substantially, or they are adjacent or located at low, and in particular very low, distance from one another. Here we mean "adjacent", which is immediately adjacent or adjoining. Here, the term "located at a short distance" means a distance of the order of one centimeter for walls 5 and 6 having dimensions of the order of 10 cm to 60 cm, as indicated above. It is understood that these numerical data are only exemplary and in no way limiting. They express that the stitching zone 12 and the n analogous output ports 10 coincide with the end edge 18 of the pocket 1 in its folded configuration, or that they are very close to one another.

The preceding embodiments of the folding zone 12 are only exemplary and in no way limiting.

The Figures 1 to 7 illustrate a first embodiment, in which the n analogous output ports 10 are distributed at least substantially uniformly and at least substantially regularly spaced apart from each other in the whole of the quilting zone 12.

The Figures 8A and 8B illustrate a second embodiment, wherein the n analogous output ports 10 are distributed at least substantially uniformly not in the whole of the quilting zone 12 as in the first embodiment, but in all of several quilting sub-zones , in this case two sub-areas 12a and 12b. This embodiment is only exemplary and not limiting, the number of sub-areas 12a, 12b ... may be different.

Each quill sub-zone 12a, 12b ... has the characteristics of the quilting zone 12, namely is continuous, delimited by output ports 10 or their proximity, and linearly extended ( figure 8A ) or surfacically extended ( Figure 8B ) and in particular linearly extended or surfacically extended linearly, along a sub-sewing segment 13a, 13b ... ( figure 8A ). In the embodiment shown on the figure 8A such sub-sewing segments 13a, 13b are substantially rectilinear. In other embodiments, one or more stitching sub-segments 13a, 13b comprises at least one substantially rectilinear section.

In the realization of the figure 8A , the sub-sewing segments 13a and 13b are located at least substantially parallel to each other. In another embodiment, the stitching sub-segments 13a, 13b ... are at least substantially an extension of each other.

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

In the realization of the Figure 8B the two sub-areas 12a and 12b are spaced from each other along the segment 13 of the stitching zone 12.

For each quill sub-zone 12a, 12b ..., it is possible to have the characteristics previously described for the folding zone 12. Thus, the output ports 10 may be at least substantially regularly spaced from each other in each sub-zone. -pitching area 12a, 12b ...

The different sub-areas 12a, 12b ... constituting together the quilting zone 12 are separated from each other by zones without quilting 19. By unpitched zone 19, the fact that in this zone there is no no queuing output port 10, which does not exclude the presence of another port, such as for example an input port 9 as shown on the figure 8A .

Where appropriate, at least some of the stitching sub-areas 12a, 12b ..., in particular all the stitching sub-areas 12a, 12b ..., are located in the vicinity of each other.

In the realization of the figure 8A , there are provided two sub-areas 12a and 12b linearly extended, arranged opposite one another, parallel to each other and in the vicinity of one another. This embodiment makes it possible to interpose the lower end edge 18 of the pocket 1 in its folded configuration between the two sub-zones 12a and 12b, parallel to the sub-sections 13a and 13b.

In the realization of the figure 8A two sub-zones 12a and 12b are provided which are surface-spaced apart from each other along the segment 13 of the quilting zone 12, so as to provide a non-quilting zone 19 between them, in which the port of entry 9.

The described achievements are only exemplary and in no way limitative as to the number, shape, relative layout of sub-areas 12a, 12b ..., the number and the relative arrangement in each sub-area of exit 10.

The arrangement of the at least one passage and mounting opening 14 and the output ports 10, in relation to the output ports 10, is now described.

In the realization of Figures 1 to 7 , there is provided a single and single opening passage and mounting 14 common to the plurality of n similar output ports 10. Such an arrangement The construction is well suited in the case where the n analog output ports 10 are distributed throughout the quilting zone 12, which is in one piece, without sub-zones, in the sense that has been previously described.

In another embodiment, it may be provided that a passage and mounting aperture 14 is common not to the plurality of n analog output ports 10, as before, but only to a portion of the output ports 10 of the plurality of n similar output ports 10. Such a constructive arrangement is well suited in the case where the quilting zone 12 has a plurality of stitch sub-zones 12a, 12b ... Thus, it can be provided for as many passage openings and In this case, each exit opening and mounting opening 14 of the output port 10 is associated with a stitch sub-zone 12a, 12b. .. Thus, in the case of Figures 8A and 8B two passage and mounting openings 14a and 14b corresponding to the two sub-zones 12a and 12b are provided.

In the realization of the figure 9 it is provided that at an output port mounting and port opening 14 there is associated a single output port 10 of the plurality of n analog output ports 10.

The embodiments described with regard to the arrangement of the opening passage and mounting 14 and the output ports 10 are only exemplary and not limiting.

The arrangement of a securing plate 17 in relation to one or more of the output ports 10 is now described.

In the realization of Figures 1 to 7 , there is provided a single connecting plate 17 common to the plurality of n analog output ports 10. Such a constructive arrangement is well suited in the case where the n analog output ports 10 are distributed throughout the quilting area 12, which is in one piece, without sub-areas, as previously described.

In another embodiment, it may be provided that a securing plate 17 is common not to the plurality of n analog output ports 10, as above, but only to a portion of the output ports 10 of the plurality of n ports of Analogous output 10. Such a constructive arrangement is well suited in the case where the stitching zone 12 has several stitching sub-zones 12a, 12b ... Thus, it is possible to provide as many fastening plates 17 as of sub-zones. In this case, each fastening plate 17 is associated with a stitching sub-zone 12a, 12b ... Thus, in the case of Figures 8A and 8B , there is provided two fastening plate 17 corresponding to the two sub-areas 12a and 12b.

In the realization of the figure 9 , it is provided that a connection plate 17 is associated with a single output port 10 of the plurality of n analog output ports 10.

According to the embodiments and according to the arrangement of a securing plate 17 in connection with one or the output ports 10, a securing plate 17 has a single opening 17b for the n analog output ports 10 or a 17b is not common to the plurality of n analog output ports 10, as previously, but only to a portion of the output ports 10 of the plurality of n analog output ports 10 or 17b is associated with a single port of output 10 of the plurality of n analog output ports 10. Where appropriate, the fastening plate may comprise a middle portion in the form of a grid and a solid peripheral portion for the fastening and the fixed and sealed connection.

The embodiments described with regard to the arrangement of a securing plate 17 in relation to one or more of the outlet ports 10 and the arrangement of the opening or openings 17a are only exemplary and in no way limiting.

According to one embodiment, the fastening plate 17 has a certain rigidity, which allows a certain holding of the tube section 16. On the other hand, according to another embodiment illustrated by the figure 9 , the inner face 17a or the central free portion of the inner face 17a around the passage which is provided with the connecting plate 17 is shaped to facilitate the emptying, and in particular the complete emptying, of the biopharmaceutical product. For example, the inner face 17a may be funnel-shaped or comprise drainage channels.

The draining / filling tube 16 is designed to be communicatively associated with its distal end 16b to an elementary container 2 to be filled with the biopharmaceutical product in the bag 1. In one embodiment, the tube 16 for emptying / filling has at its distal end 16b, a nozzle 20 or a similar dispensing member such as filling needles. This combination is designed to be removable, the distal end 16b to be dissociated from the elementary container 2 when filled, then associated with another container 2 to fill and so on.

The dispensing assembly may also comprise means for association / dissociation of the nozzles 20 or analogous distribution members which are filled with the tubes 16 of emptying / filling. These means may be, in whole or in part, manual or mechanized, if necessary programmed in connection with the operation or programming of the filling and the supply and evacuation of the containers 2.

For this purpose, the dispensing assembly also comprises, on the one hand, means for feeding a plurality, in particular n, receptacles not yet containing the desired dose of biopharmaceutical product, and, on the other hand, , means of evacuation of a plurality, in particular n, receptacles containing said dose of biopharmaceutical product. These means can be, in whole or in part, manual or mechanized, if necessary programmed in connection with the operation or programming of the filling.

As already indicated, the dispensing assembly also comprises a stop member (such as a chuck) or a drive-dosing or withdrawal / dosing device (such as a pump, such as a peristaltic pump or an RDP pump or the like functionally) 21 with which cooperates each tube 16 draining / filling. Such means 21 may be programmed or controlled depending on the desired filling and the conditions and modalities thereof.

In one embodiment, it is provided that the means 21 are not specific to each of the tubes 16 for emptying / filling but common to several tubes 16.

The embodiments described with regard to the fastening plate 17 and the pipe section 16 are only exemplary and in no way limiting.

The various configurations and states of the flexible distribution bag 1 are now described.

The dispensing bag 1 is, when necessary, in an unfolded configuration ( Figures 1 to 4 ) in which the two opposite walls 5 and 6 are extended. In this configuration, the pocket 1 is, when necessary, either in an empty state where the interior space 3a is empty of biopharmaceutical product ( Figures 1 to 4 ) - for example once the flexible bag 1 has been made - either in a filled state where the interior space 3a is filled with biopharmaceutical product - for example in a first variant of implementation of the flexible bag 1 -.

The dispensing bag 1 is, when necessary and for its implementation of emptying the biopharmaceutical product in the interior space 3a, in a folded configuration ( Figures 5 to 7 ) in which the two opposite walls 5 and 6 are folded on themselves in the folding zone 8 with the stitching face 5 located outside the fold. In this folded configuration, the dispensing pocket 1 comprises, in the folding zone 8, the end edge 18 at or near the location of the stitching zone 12 and the n analog output ports 10. In this folded configuration, the dispensing bag 1 is, when necessary, in a filled state where the interior space 3a is filled with biopharmaceutical product ( Figures 5 to 7 ) - for example at the moment when the bag will be emptied - in an empty or emptied state, respectively, where the interior space 3a is empty or empty, respectively of the biopharmaceutical product - for example before filling the flexible bag of the biopharmaceutical product in a second variant of implementation or after emptying, respectively -.

The arrangement of the stitching zone 12 and the folding zone 8 on the stitching face 5 is now described.

Therefore, it is important that the stitching zone 12 - which is not necessarily identified as such on the pocket 1 - and the folding zone 8 are located judiciously on the face of 5. In carrying out the Figures 5 to 7 , the quilting zone 12 and the folding zone 8 are located at or near the central zone 5b of the quilting face 5. For example, the quilting zone 12 and the folding zone 8 are located at the place or in the vicinity of the central axis AA of the stitching face 5 situated equidistant from the two opposite peripheral sections 7a of the stitching face 5. With such an embodiment, the pocket 1 in its folded configuration has a symmetrical general disposition relative to a vertical plane of symmetry P (parallel to the plane of Figures 5 and 6 and identified on the figure 7 ). Thus, the interior space 3a is then subdivided into two interior subspaces 3aa and 3ab, of equal or substantially equal volumes. On the other hand, the two peripheral sections 7a come into coincidence or substantially in coincidence and constitute the upper end edge 22 of the pocket 1 in its folded configuration ( Figures 5 to 7 ).

According to a development, it is expected that the flexible bag 1 comprises means capable of maintaining a permanent communication between the two inner subspaces 3a, 3b. These means may be spacer type or they may consist of allowing the evacuation of gas during the emptying of the bag 1 of the biopharmaceutical product.

These achievements are only exemplary and in no way limiting.

The arrangement of the input port or ports 9 with respect to the envelope 3 is now described.

In the realization of Figures 1 to 6 , it is expected that the flexible bag 1 has two input ports 9 located on the stitching wall near the stitching zone 12, here being located on either side of the stitching zone 12 by being more near the large peripheral section 7b close to the stitching wall 5 than the exit ports 10.

In the realization of the Figure 8B , it is expected that the flexible bag 1 has a single input port 9 located at the same place of the stitching area 12, here between the two stitching sub-areas 12a and 12b.

This type of constructive arrangement makes it possible to fill the inner space 3a of the biopharmaceutical product while the flexible bag 1 is in its folded configuration, the biopharmaceutical product being injected into the two inner subspaces 3aa and 3ab, by the lower end. 18 of the bag 1, which avoids the foaming effect that would be obtained with a biopharmaceutical product having a foaming power that is injected into the flexible bag from above.

In the realization of the figure 8A , it is expected that the flexible bag 1 comprises a single inlet port 9 located at a location distinct from the stitching zone 12, and more particularly away from the stitching zone 12, for example located in the vicinity or near the a securing section close to the peripheral section 7b, while being situated on the stitching wall 5.

In the realization of the figure 10 two inlet ports 2 are provided, located at a median height of the pocket in its folded configuration.

These achievements concerning the arrangement - number and layout - of the input port or ports 9 are only exemplary and in no way limiting.

The arrangement of the gas inlet / outlet port (s) 11 is now described.

One or more of these ports 11 are intended either to enable the introduction from the outside of the flexible bag 1 into the interior space 3a, above the biopharmaceutical product, of a gas for storing this product or to allow the evacuation of gas from the interior space 3a towards the outside of the flexible bag 1 during the emptying of the latter, which prevents the pocket 1 from tightening on itself, as this may hamper the emptying of the product biopharmaceuticals.

One or such ports 11 are located at a remote location, and in particular clearly spaced, of the quilting zone 12, for example are located in the vicinity of or near a securing section near the peripheral portion 7a.

According to the embodiments, such a port 11 is located on the stitching wall 5 or on the wall 6 opposite to the stitching wall 5.

These achievements concerning the arrangement - number and arrangement - of the ports 11 of gas inlet / outlet are only exemplary and in no way limiting.

According to a development, it is provided that the zones 5a and 6a of the quilting face 5 and of the opposite face 6 which are adjacent to the section 7a of the pocket 1 and which, in the flexible pouch 1 in its folded configuration are adjacent to the upper end edge 22 and opposed to the lower end edge 18 form suspension zones of the pocket 1 in its folded configuration. Such suspension zones 5a and 6a may include suspension members 23, such as holes or projections adapted to removably cooperate with complementary suspension members, such as hooks or stems forming part of the machine or the installation in which the pocket is implemented for its emptying and filling of the elementary containers 2. Such a removable suspension embodiment with holes or projections 23 and hooks or brackets 23a is part of the general knowledge of the skilled person pockets here considered. According to another embodiment, the suspension members 23 are provided only on one of the faces 5 or 6, provided that means are provided for holding the two opposite walls 5 and 6 folded on themselves when the pocket 1 is in the folded configuration. With suspension means 23 and 23a as described, the flexible bag 1 in its folded configuration is positively maintained so that the end edge 18 of the bag 1 located at or near the folding zone 8 and of the quilting zone 12 is the lower edge of the pocket 1 and the inner space 3a is placed above, of so as to allow the emptying of the biopharmaceutical product from the interior space 3a through the exit ports 10.

Instead of the holding means of the flexible bag 1 thus folded and disposed in the form of the suspension means 23 and 23a described above, there may be provided means for maintaining the equivalent pocket, structurally different but providing the same function. For example, it may be a rigid container having in the lower part at least one passage for the n analog output ports, whose shape corresponds to that of the pocket filled with biopharmaceutical product.This container may incorporate plates lateral pressure on the faces 5 and 6.

The invention includes an assembly comprising a flexible bag 1 as has been described holding means of the flexible bag 1 in its folded configuration so that the end edge 18 is placed horizontally and in the lower position and that the end edge 22 is placed horizontally and in the upper position, the pocket 1 being placed vertically with its vertical plane of symmetry P. Thus, it is possible to ensure the emptying of the biopharmaceutical product by the output ports 10 by simple gravity, or if necessary forcibly and assisted by exerting compression on both sides 5 and 6 of the bag 1.

Thus, depending on the case, the holding means are suspension means 23b able to cooperate with suspension members 23a of the pocket or lateral restraining means, such as a rigid container comprising in the lower part at least one passage for the n analog output ports.

These achievements concerning the maintenance and in particular the suspension of the flexible bag 1 are only exemplary and in no way limiting.

According to another development, it is provided that the flexible bag 1 comprises means 24 able to hold the two opposite walls 5 and 6 folded on themselves when the bag 1 is in the folded configuration, so as to prevent the bag from unfolds.

These holding means 24 may be constituted by the suspension members 23 of the bag 1, the suspension of the bag 1 to the complementary suspension members 23a may be such that the two periphery sections 7a of the bag 1 are maintained adjacent or contact each other. This effect is obtained because of the weight of the pocket 1 on the complementary suspension members 23a via the suspension members 23 of the pocket 1. Where appropriate, the complementary suspension members 23a are provided with notches or protrusions avoiding that the two periphery sections 7a of the pocket 1 depart inadvertently.

These holding means 24 may be holding members complementary to each other, provided on the casing 3 and in particular on the face 6 which is inside the fold of the pocket 1 in its folded configuration. Such additional holding members are reversibly or irreversibly maintained depending on the intended applications and they may be, for example, in the form of self-gripping strips such as those known under the trademark VELCRO® or buttons type snap .

These achievements concerning the maintenance of the pocket 1 in the folded state are only exemplary and in no way limiting.

A flexible pouch as just described is most often intended to be implemented in a sterile environment and for this reason it is sterile, having rendered sterile by a suitable treatment such as for example γ radiation. Such pocket sterilization treatment for biopharmaceutical use is part of the general knowledge of those skilled in the art.

The realization of a pocket 1 as it has been described can be deduced from the very structure of the pocket.

In this process, there is a plastic film capable of being cut and secured to itself and to form the flexible pocket walls constituting the envelope 3, in particular the walls 5 and 6.

There are also components for constituting the ports 9 and 11 and especially the analog output ports 10.

There are also film cutting means and fastening means, in particular welding means.

Then, the film is cut to the desired shape of the walls of the pocket, in particular the two opposite walls 5 and 6.

The aperture wall and / or apertures 14, 14a, 14b ... are also cut in the stitching wall 5, for the n similar output ports 10.

Then, the walls 5 and 6 are fixedly and sealingly secured together to form the casing 3 and the outlet ports 10 at the stitching wall 5 around the opening or openings 14, 14a, 14b.

Thus, a flexible bag 1 as described in its unfolded configuration and in the empty state of biopharmaceutical product is obtained.

According to a particular embodiment of the method, at an outlet port 10, a draining / filling tube 16 is communicatively associated at its proximal end 16a and a securing plate 17 and the securing plate 17 is secured to one another. in particular by gluing or welding, in a fixed and sealed manner to the stitching wall 5 around a passage opening and mounting opening 14 of the exit port 10.

According to another embodiment which can be combined with the preceding one, at an input port 9, a filling / feeding tube 25 is communicatively associated with its proximal end 25a. In particular, the pocket 1 comprising a plurality of input ports 9, is associated with each of them a first section 29 tube filling / feeding at its proximal end 25a, and it is associated in a communicating manner the plurality of first sections of filling / feeding tube 29 at their distal ends 29a at the proximal end 30a of a second common section of filling / feeding tube.

These embodiments of the method of maintaining the pocket 1 are only exemplary and not limiting.

The invention also relates to the dispensing assembly of a dose of a biopharmaceutical product in a set of receptacles 2, such as containers 2.

This dispensing assembly comprises on the one hand a dispensing pouch 1 as it has been described, this one being for single use and being in particular in the filled state of a biopharmaceutical product.

The dispensing assembly also comprises the means for holding the pocket 1, such as the suspension members 23a, or any other device or arrangement providing the same result, namely that the end edge 18 located at the place where close to the folding zone 8 is the lower edge of the pocket 1, the inner space 3a being placed at the top.

The dispensing assembly also comprises means for communicatively connecting the distal end 16b of the emptying / filling tubes 16 to the containers 2.
The dispensing assembly also comprises the means of stopping discharge or withdrawal / metering 21 already mentioned.

In one possible embodiment, the dispensing assembly may also include means for communicatively connecting the distal end 25b of the or each filling / supply tube to a biopharmaceutical product supply 26.

In this case, the dispensing assembly may comprise supply or feed / dosing stop means 28, in particular programmed or controlled, functionally associated fill / feed tube (s) for filling the inner space 3a of the bag 1 with the biopharmaceutical product from the biopharmaceutical product feed 26.

As indicated, the means for stopping evacuation or withdrawal / metering 21 may comprise a stop clamp or a pump set for the distribution of successive doses of biopharmaceutical product. On the other hand, the feed stop or feed / metering means 28 may comprise a pump, such as a peristaltic pump or an RDP pump or another functionally similar pump.

According to one embodiment, the dispensing assembly adapted to the case where the p containers 2 are filled with several successive contents of pocket 1, the distribution assembly is adapted accordingly and it is expected that it comprises, first instead, means for detecting the exceeding of a minimum quantity and a maximum quantity of biopharmaceutical product in the interior space 3a of the bag 1.

This dispensing assembly comprises, secondly, means for controlling the means for stopping discharge or withdrawal / metering 21 and means for stopping supply or feed / dosing 28 responsive to said means for detecting the exceeded. Thus, when the quantity of biopharmaceutical product in the inner space 3a of the bag 1 reaches the minimum quantity, the control means control the operation of the supply or feed / dosing stop means 28 associated with the tube Filling / feeding to fill the inner space 3a of the bag 1 with the biopharmaceutical product from the feed 26 to a biopharmaceutical product. Whereas, when the amount of biopharmaceutical product in the inner space 3a of the bag 1 reaches the maximum amount, the control means controls the operation of the supply or feed / dosing stop means 28 to stop filling the inner space 3a of the pocket 1 with the biopharmaceutical product from the feed 26 into a biopharmaceutical product.

According to one development, the containers 2 are located respectively inside and outside of an aseptic chamber. Depending on the case and the achievements, the pocket 1, itself, is located either inside or outside this aseptic chamber. The wall of the aseptic chamber is thus traversed respectively by the tubes 16 of emptying / filling or by a tube 25 filling / feeding.

The method for implementing such a flexible bag 1, that is to say the distribution of the biopharmaceutical product, is now described. Indeed, by implementation it is meant that, starting from a flexible bag 1 in its unfolded configuration and in the empty state of a biopharmaceutical product, the biopharmaceutical product is distributed by the plurality of n similar output ports. 10, in particular to dispense the biopharmaceutical product into the elementary receptacles 2.

Initially, there is a flexible bag 1 having an unfolded configuration and in the empty state. The biopharmaceutical product is also available.

There are also containers 2 not yet containing the desired dose of biopharmaceutical product.

Then, in the first place, the pocket is folded in its fold zone 8 so that the two opposite walls 5 and 6 are folded on themselves with the face of the stitching wall 5 located outside the fold. forming an end edge 18 of the folded pocket, at or near the location of the stitching area 12 and the n output ports 10. Thus the pocket is brought into its folded configuration.

In the second place, the inner space 3a of the pocket is filled with the biopharmaceutical product, via the at least one input port 9.

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

Fourthly, the end edge 22 is positioned and maintained so that it is and remains the upper edge of the dispensing pocket 1, thanks to the suspension members 23a, more generally maintaining the pocket 1, implemented so that the end edge 18 of the pocket 1 located at or near the folding zone 8 is its lower edge, the interior space 3a being placed at above.

In this situation, it is possible, at the desired moment, to evacuate the biopharmaceutical product through the n exit ports 10, and the n associated draining / filling tubes 16, simultaneously, and to dispense the same dose of product. biopharmaceutical in the first plurality of containers 2 by the nozzles 20, thanks to the combined effect of gravity and means 21 (in a dosage and drive function). Thus, a first plurality of containers 2 containing said desired dose of biopharmaceutical product is obtained.

Then, while preventing the evacuation of the biopharmaceutical product by the n output ports 10, by means 21 (in a stop function), the first plurality of containers 2 containing at this time the dose of biopharmaceutical product, and it brings a second plurality, in particular of n, containers 2 not yet containing the dose of biopharmaceutical product, through the means of supply and discharge of the dispensing assembly.

The process is repeated with this second plurality of containers 2, and so on until the containers (2) have been filled.

According to the embodiments, firstly the bag 1 is folded and then the inner space 3a of the bag 1 is filled with the biopharmaceutical product, first of all the inner space 3a of the bag is filled. 1 with the biopharmaceutical product and then the pouch 1 is folded.

In all cases, the pocket 1 being in the folded configuration and in the filled state the end edge 18 is disposed and maintained horizontally and in the lower position and the end edge 22 placed horizontally and in the upper position, the pocket 1 being placed vertically with its vertical plane of symmetry P.

The process which has just been described has been carried out in the case where it is carried out in several passes, each time for a number n of containers 2, all the p containers 2 concerned being larger, in particular much larger. that n.

Of course, the method can be considered in the case where p = n.

On the other hand, the method may comprise two variants.

According to a first variant, the inner space 3a of the pocket is filled with the quantity necessary to fill all the containers 2. These can therefore be filled with a single pocket contents 1. In this case, a Once the inner space 3a of the pocket 1 has been filled with biopharmaceutical material, there is no need to consider reloading it as a biopharmaceutical product. And that is why the input port 9 can remain closed.

According to a second variant, the inner space 3a of the pocket is filled with an amount which is only a fraction of that necessary to fill all the containers. In this case, it is intended to fill the containers 2 with several successive contents of pocket 1. In a preferred embodiment, it is several successive contents of the same pocket 1. In this case, and thanks to the distribution assembly adapted accordingly, in a first step, with the detection means that comprises the distribution assembly, it detects the exceeding of a minimum quantity and a maximum quantity of biopharmaceutical product located in the interior space 3a of the pocket 1.

Then, in a second step, depending on the detection carried out and with the control means that the distribution assembly comprises, the means for stopping evacuation or withdrawal / metering associated with the tubes 16 emptying / filling and the supply or feed / dosing stop means 28 associated with the filling / feeding tube (s) so that, when the quantity of biopharmaceutical product in interior space 3a of the bag 1 reaches the minimum quantity, it controls the operation of the supply or feed / dosing stop means 28 associated with the filling / feeding tube (s) to fill the space 3a interior of the pocket 1 with the biopharmaceutical product from the biopharmaceutical product feed and that, when the quantity of biopharmaceutical product in the interior space 3a reaches the maximum quantity, the stop means is controlled feeding or feeding / dosing 28 to stop filling the inner space 3a with the biopharmaceutical product coming from the feed 26.

Claims (15)

1. 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.
2. Bag (1) according to claim 1, 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 1/5^th, particularly less than 1/10^th, even more particularly less than 1/20^th, 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.
3. Bag (1) according to any of claims 1 to 2, 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.
4. Bag (1) according to any of claims 1 to 3, 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).
5. Bag (1) according to any of claims 1 to 4, 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.
6. Bag (1) according to any of claims 1 to 5, 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).
7. Bag (1) according to any of claims 1 to 6, 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).
8. Bag (1) according to any of claims 1 to 7, 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.
9. Bag (1) according to any of claims 1 to 8, 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.
10. Bag (1) according to any of claims 1 to 9, having an unfolded configuration in which the two opposite walls (5 and 6) are stretched out.
11. Bag (1) according to any of claims 1 to 9, 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.
12. 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 11, 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).
13. Distribution assembly according to claim 12, 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).
14. Distribution method making use of a bag (1) for distributing a dose of biopharmaceutical product according to any of claims 1 to 11, for the purposes of distributing a same dose of a biopharmaceutical product through the 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 10 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 according to claim 22; 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).
15. Method for creating a distribution bag (1) according to claim 10, 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.

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