Fluid material container for aseptic manufacturing processes

Abstract

The disclosure provides a flexible container configured to hold a fluid for pressurized dispensing, the flexible container including: a first flexible wall and a second flexible wall that are hermetically sealed together to form an internal space configured to hold the fluid; at least one outlet port configured for outputting the fluid from the internal space; and an enclosed spacer extending from the at least one outlet port into the internal space of the flexible container, the enclosed spacer configured to provide a fluid path from the internal space to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

Description

[0001] TITLE: FLUID MATERIAL CONTAINER FOR ASEPTIC MANUFACTURING PROCESSES

[0002] Description

[0003] BACKGROUND

[0004] Process automation as well as up- and downscaling of mixing processes are tasks regularly dealt with in various fields of biotechnology and medicine.

[0005] Systems for the production of mixed fluids or products based on the combination of two or more components need a source of liquid raw material, supply lines, a chamber in which the mixing or reaction takes place and an outlet for harvesting the product. The chamber often represents the heart of such systems.

[0006] In certain technological areas, such as the pharmaceutical manufacturing processing area, the amounts of product to be produced may be in the milliliter scale. Accordingly, it is necessary to make apparatus systems available, capable of producing goods on such a scale. This is particularly relevant for the preparation of mixed pharmaceutical fluids, for example in the field of personalized medicine. Particular attention has to be spent on designing processes and apparatuses that optimize production efficiency, inter alia, by minimizing the amount of unmixed or unreacted substrates residues, which are generally very expensive, particularly in cases of products that are manufactured on a milliliter scale.

[0007] Such apparatus may mix two liquids comprising a static mixer and a first and second feed module for feeding the two liquids into the mixer. The feed modules comprise chambers for accommodating flexible containers that hold the liquids to be mixed and that can be pressurized. The liquids are forced through the static mixer when the chambers comprising the flexible containers are pressurized. Pressurization is achieved by pressurized gas stored in pressure reservoir chambers that are connectable to the chambers holding the flexible containers.

[0008] Accordingly, the flowing of the liquids into the static mixing device and the collection of the so-obtained product in the corresponding containers is driven by applying pressure on the external surface of the flexible containers, so that all liquids or product contacting parts can be provided as sterile disposables.

[0009] The flexible containers of the apparatus described above are containers that are adapted to hold fluid materials and may exhibit a high degree of flexibility, similar to infusion bags. The flexible containers are typically made of a front and a back wall made of a polymeric material, the two walls being sealed to each other along their edges so as to define the internal space of the flexible containers.

[0010] In order to generate, by means of external pressure, the flow of a fluid material from a container towards a processing unit, such as a static mixer, the material making the substrate containers must be sufficiently flexible to allow adequate compression of the container walls, so that the fluid material is urged through its outlet ports and the conduits towards the processing unit.

[0011] For the choice of the container materials, special care has to be paid to design the structure in such a way that the two walls of the container are prevented from adhering to each other, particularly when most of the fluid material has already left the container. Adhesion of the two walls would inhibit the flow of some residual product out of the container. This would inevitably lead to dead volumes within the container and, accordingly, to wasted residues of the fluid material contained therein, thus leading to less efficiency of the overall manufacturing process. This problem is further accentuated by the force of gravity which is applied on the residual fluid material in the lower part of the flexible container. This is particularly the case when the flexible container is operated in its vertical position.

[0012] It is thus an object of the present disclosure to provide alternative or additional container structures and design which enable to overcome the problems mentioned above and which are suitable to be used in apparatus, devices or apparatus components like that described above, in particular for the manufacture of small quantities of products in a reliable and efficient way.

[0013] Further objects of the disclosure will be clear on the basis of the following description, disclosure, embodiments, and claims.

[0014] SUMMARY

[0015] In a first aspect, the disclosure relates to a flexible container suitable for use in an apparatus system for the manufacture of pharmaceutical products, comprising an internal space for holding a fluid material, the internal space being defined by a flexible front wall and a flexible back wall which are hermetically assembled together by means of a sealed edge substantially surrounding the internal space, at least one outlet port to enable fluid communication between the internal space and the external environment of the flexible container, wherein the flexible container further comprises a means positioned within the internal space for preventing complete collapse of the flexible container.

[0016] In a second aspect, the disclosure provides for an apparatus adapted for receiving and holding at least two flexible containers as described above, wherein the first flexible container contains a first substrate and the second flexible container contains a second substrate, the apparatus further comprising means for forcing the substrates to flow from the first and the second flexible container into a processing unit device, optionally a mixing device or a chemical reactor, to process the first and second substrates into a liquid product, wherein said means is adapted for exerting pressure, optionally by means of a pressurized gas, on the external surface of the first and the second flexible container.

[0017] In another aspect of the disclosure, a flexible container for use in an apparatus system for the manufacture of pharmaceutical products is provided, the flexible container comprising: an internal space for holding a fluid material, the internal space being defined by a flexible front wall and a flexible back wall that are hermetically assembled together by a sealed edge substantially surrounding the internal space, and at least one outlet port for fluid communication between the internal space and an external environment of the flexible container, wherein the flexible container further comprises a non-hollow spacer positioned within the internal space, the non-hollow spacer configured to prevent complete collapse of the flexible container.

[0018] In yet another aspect of the disclosure, a flexible container configured to hold a fluid for pressurized dispensing is provided, the flexible container comprising: a first flexible wall and a second flexible wall that are hermetically sealed together to form an internal space configured to hold the fluid; at least one outlet port configured for outputting the fluid from the internal space; and an enclosed spacer extending from the at least one outlet port into the internal space of the flexible container, the enclosed spacer configured to provide a fluid path from the internal space to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

[0019] BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 depicts a frontal view of a first embodiment of a flexible container in accordance with the present disclosure.

[0021] Figure 2 depicts a frontal view of a second embodiment of a flexible container in accordance with the present disclosure. Figure 3 depicts a frontal view of a third embodiment of a flexible container in accordance with the present disclosure.

[0022] Figure 4 depicts a frontal view of a fourth embodiment of a flexible container in accordance with the present disclosure.

[0023] Figure 5 depicts a frontal view of a fifth embodiment of a flexible container in accordance with the present disclosure.

[0024] Figure 6 depicts a frontal view of a sixth embodiment of a flexible container in accordance with the present disclosure.

[0025] Figure 7A depicts a frontal view and Figure 7B depicts a partial cross-sectional view of the flexible container in accordance with the present disclosure.

[0026] Figures 8A, 8B, 8C, and 8D depict aspects of the enclosed spacer in accordance with the present disclosure in frontal and cross-sectional view.

[0027] Figure 9 depicts a cross-sectional view of the flexible container comprising the enclosed spacer in accordance with the present disclosure.

[0028] Figures 10A, 10B, and IOC depict side views of aspects of the enclosed spacer in accordance with the present disclosure.

[0029] Figures 11A, 11B, and 11C depict frontal views of aspects of the flexible container comprising enclosed spacer in accordance with the present disclosure.

[0030] Figures 12A and 12B depict frontal views of aspects of the internal space of the flexible container.

[0031] Figures 13A and 13B depict frontal views of aspects of the flexible container comprising a port boat.

[0032] Figures 14A and 14B depict cross-sectional views of the port boat and enclosed spacer.

[0033] DETAILED DESCRIPTION

[0034] In one aspect, the present disclosure provides a flexible container suitable for use in an apparatus system for the manufacture of pharmaceutical products, comprising an internal space for holding a fluid material, the internal space being defined by a flexible front wall and a flexible back wall which are hermetically assembled together by means of a sealed edge, substantially surrounding the internal space, at least one outlet port to enable fluid communication between the internal space and the external environment of the flexible container, wherein the flexible container further comprises a means positioned within the internal space for preventing complete collapse of the flexible container.

[0035] For the purpose of the present disclosure, the flexible container according to the present disclosure will be described in a vertical operating position, whereby the at least one outlet port is positioned on the upper side of the sealed edge and the internal space comprises a lower, a middle and an upper part Under such circumstances, the fluid material held in the flexible container may be urged through the at least one outlet port in an anti-gravity- direction, i.e., in a direction which is substantially the opposite of (i.e., at an angle of about 180° to) the direction towards which the gravity force would naturally pull the fluid content The flexible container according to the present disclosure can however be operated in any position other than the vertical one, in function of the specific configuration of the apparatus in which it is used.

[0036] As used herein and unless the context dictates otherwise, a fluid material, sometimes also simply referred to as a fluid, is a liquid material.

[0037] Under "complete collapse” it is meant, in accordance with the present disclosure, that the front and back walls of the flexible container adhere, at least partially, to each other, for example upon applying external pressure thereon, or by creating vacuum in the internal space. This may happen when only a small amount of fluid material is present within the internal space of the flexible container. Under such circumstances, part of the residual fluid material, particularly in the lower part of the internal space, may remain entrapped in so- called "dead zones” and can no longer leave the internal space through the at least one outlet port. Accordingly, complete collapse may also be understood as a situation in which the front wall and the back wall of the container come into contact with each other such as to entirely obstruct any flow path for the residual fluid to the outlet port The means for preventing complete collapse may therefore also be understood as a means for preserving or maintaining an open fluid path between a lower part of the internal space where residual fluid material resides and the outlet port at the upper side of the flexible container.

[0038] The flexible front and the flexible back wall may be hermetically assembled to form a sealed edge by welding or other technologies.

[0039] The inventors have found that the flexible container in accordance with the present disclosure is useful throughout a wide range of mixing and manufacturing processes at different scales. It is particularly useful for aseptically mixing or reacting fluid materials on a milliliter scale, by avoiding the use of pumping systems. Accordingly, the flexible container of the present disclosure is particularly useful in a mixing or manufacturing apparatus where external pressure, e.g., gas pressure, is used for urging the fluid content out of the flexible container, in particular when it is desirable that the fluid exits the container in an anti-gravity direction of flow, and / or when it is desirable that any gas entrapped in a fluid-filled flexible container is removed from the container before the fluid is forced out. This inventive construction prevents the front and back walls from adhering to each other completely under the effect of externally applied pressure, particularly when some or most of the fluid material has already left the container. As said, adhesion of the container walls to each other, particularly in the middle zone of the internal space, would lead to the obstruction of the fluid pathway from the bottom of the internal space to the outlet port of the container, thus entrapping residual quantities of the fluid within the container. Hence, the flexible container according to the present disclosure enables optimizing the use of the fluid material by minimizing or even eliminating dead volumes of wasted residual material. This is particularly relevant in manufacturing processes involving very expensive substrates, such as sophisticated pharmaceutical active ingredients, vaccine components and the like, where it is not affordable to waste any amount of material, as small as it may be.

[0040] As mentioned above, the flexible container according to the present disclosure is particularly suitable for use in apparatus and systems where the fluid material is urged out of the container by applying external pressure on the walls of the flexible container. Such systems and apparatus which do not require pumps are particularly suitable for manufacturing processes under aseptic conditions, especially for small batch sizes. However, the flexible container according to the present disclosure is also suitable in apparatus and systems where the fluid material is urged out of the container by other means like, for example, a pump system, where structural collapse is triggered by the generation of vacuum in the internal space of the flexible container.

[0041] The flexible container according to the present disclosure is particularly suitable for holding substrates or other materials which are consumed during a manufacturing or mixing process. For example, the container according to the present disclosure is particularly suitable for holding the substrates or components which are subsequently conveyed into a mixer unit or a reactor for further processing. In other words, the flexible container according to the present disclosure is particularly suitable in processes where its fluid material content is reduced over time and, accordingly, the risk of structural collapse when the flexible container is almost empty arises. However, the flexible container according to the present disclosure can be used for other purposes and whenever the risk of creating dead-zones within the internal space arises.

[0042] The flexible container according to the present disclosure is preferably intended for single use.

[0043] In respect of dimensions, the flexible containers according to the present disclosure may have any internal volume suitable for a given application. For example, the substrate containers according to the present disclosure may have a volume varying between about 10 mL to about 3,000 mL. According to another embodiment of the present disclosure, the substrate containers may have an internal volume in the range from about 50 mL to about 1,500 mL. Other substrate containers have internal volumes of about 300±100 mL, 500±200 mL, l,000±300 mL, and l,500±300 mL, respectively.

[0044] In accordance with an embodiment of the present disclosure, the flexible front wall and the flexible back wall are made of one or more polymeric materials which are suitable for the given application and are inert with regard to the fluid material which the flexible container has to hold. The flexible front wall and the flexible back wall may have an essentially square or rectangular overall shape, but any other shape which may be more suitable under a given circumstance may also be used.

[0045] The sealed edge, which substantially surrounds the internal space of the flexible container, comprises four corner regions such that the internal space, when empty, may also have a roughly square or rectangular overall shape. In this context, a corner should be understood such as to include rounded corners. In some embodiments, the corners of the container and / or of the internal space are rounded corners. The container may be further comprising at least two through-holes provided in the sealed edge, of which a first through-hole is provided in or near a first corner region and a second through-hole is provided in or near a second corner region of the edge, and the second corner region is adjacent to the first corner region. The at least two through-holes permit the container to be held by, or affixed, in dedicated sites of a process apparatus.

[0046] In some embodiments, the flexible container comprises, in addition to the at least one outlet port, at least one inlet port Preferably, a flexible tube arranged externally with respect to the interior space is fluidically connected to the inlet port and / or outlet port In some embodiments, a first flexible tube is fluidically connected to the inlet port and a second flexible tube is fluidically connected to the outlet port. According to an embodiment of the present disclosure, the means for preventing complete collapse of the flexible container comprises a spacer which extends along or in parallel to a vertical axis V of the flexible container. In one embodiment, the spacer is a tube. In a certain embodiment, the spacer is a tube having a length which corresponds to about 90%, to about 80%, to about 70%, to about 60% or to about 50% of the [vertical) height of the flexible container. The tube may be hollow or not, e.g., a solid or filled tube (also referred to herein as an enclosed spacer). Shapes of the spacer, other than cylindrical, may also be considered if a specific situation requires so. In an embodiment of the present disclosure, the spacer may be filled to prevent the fluid material from flowing within it and may consist of any suitable, inert material such as silicone rubber. In another embodiment, the spacer is a rigid mesh tube made of any suitable, inert polymeric material. In this context, the spacer is not intended to be in fluid connection with the external environment of the flexible container and may be mounted, for example, on a dedicated port, likewise positioned on the upper side of the sealed edge of the flexible container. In such a case, the dedicated port is not an outlet port, but is hermetically sealed, thus preventing fluid communication between the internal space and the external environment of the flexible container.

[0047] According to another embodiment of the present disclosure, the flexible container comprises at least two ports, for example an outlet port and an inlet port, and the at least two ports are configured on a common platform, a so-called port boat, which is then hermetically assembled with the flexible front wall and the flexible back wall, so to form the internal space of the flexible container.

[0048] As mentioned, the spacer may be connected with, or partially inserted into a further port which may be arranged adjacent to the outlet port and / or inlet port and which is sealed towards the external environment, wherein the spacer may extend substantially along or in parallel to a vertical axis of the flexible container. It is noted that the outlet port and / or inlet port, in particular in combination with the port boat on which they are typically arranged, may contribute to a flow path which is created or kept open for fluid material to flow from a location at or near the bottom of the interior space to the outlet port at the upper side of the container. In other words, it may be possible that the spacer extending vertically from a further port towards the bottom of the interior space of the container provides one portion of the flow path which is predominantly vertical, while the port boat with the ports arranged therein provides a further portion of the flow path which is predominantly horizontal and extends from the upper end of the spacer to the relevant outlet port. In these embodiments, the port boat may also be understood as contributing to the prevention of the complete collapse of the container, as the front wall and the back wall of the container are spaced apart from each other adjacent to or near the port boat.

[0049] In a still further embodiment, the means for preventing complete collapse of the flexible container comprises a membrane which is positioned between the flexible front wall and the flexible back wall. The membrane is positioned between the two walls before hermetically assembling them to each other. The membrane may be made of any suitable inert material, not reacting in any way with the fluid material held in the flexible container. According to certain embodiments, such material may be CA (cellulose acetate), PTFE (polytetrafluoroethylene), PP (polypropylene), PVDF (polyvinylidene fluoride), glass fiber, or a silica membrane.

[0050] According to another embodiment of the present disclosure, the flexible container comprises a first outlet port and a second outlet port, a first flexible tube in fluid connection with the first outlet port and means for gas purging in fluid connection with the second outlet port. As used herein, a means for gas purging should be understood as a means for allowing gas (such as air) entrapped in a filled container to be removed from the interior space of the container, preferably before the fluid material is forced out of the container. For example, the means for gas purging may provide a flow path for gas located in an upper region of the interior space to exit the container through the second outlet port, while another flow path is provided for fluid material located in a lower region of the interior space to exit the container through the first outlet port.

[0051] In order to minimize the risk of microbiological contamination and to maintain the internal space of the flexible container aseptic, the means for gas purging may be combined with additional measures. Accordingly, one of the embodiments of the present disclosure provides for means for gas purging, comprising a second externally arranged flexible tube in fluid connection with the second outlet port, on one side, and with the first flexible tube through a tube connecting part, on the other side. The tube connecting part may be, for example, a Y- or a T-piece. Alternatively, the means for gas purging may comprise a sterile filter externally arranged at, and fluidically connected with, the second outlet port. The sterile filter would allow gas such as air to exit the container, but not allow microbiological contaminants to enter the container through the second outlet port.

[0052] In an embodiment according to the present disclosure, the means for gas purging is provided in combination with a hollow tube, also referred to as a dip tube or dip hollow tube, in fluid connection with the first outlet port and the first flexible tube, and extending substantially along or in parallel to a vertical axis V of the flexible container. The dip hollow tube provides a flow path for the fluid material residues at the lower part of the internal space and, accordingly, it may be possible to fully remove the fluid material from the flexible container.

[0053] Alternatively to the dip hollow tube, the flexible container may comprise a faceport to function as the outlet port for the fluid material to exit the container. The faceport is an outlet that is arranged in a central (or even lower) region of the flexible front wall of the container, i.e., at a distance to the upper side of the container. It provides a flow path for residual fluid material located at or near the bottom of the internal space of the container even when the front wall and the back wall have come into contact with each above the location of the faceport such as to obstruct the fluid flow within the upper region of the internal space of the container.

[0054] In accordance with another embodiment of the present disclosure, the hollow dip tube described above comprises one or more holes enabling fluid connection between the internal space and the internal part of the dip hollow tube, the one or more holes being positioned towards the end, or extremity, of the dip hollow tube which is adjacent to the at least one outlet port. Such configuration enables gas purging from the upper part of the internal space, through the hollow dip tube, the first outlet port and the first flexible tube. In such a case, a separate means for gas purging in fluid connection with the second outlet port is not necessary.

[0055] The dip hollow tube, in all its variants discussed above, may be made of any suitable material which is inert with respect to the fluid material which is held by the flexible container. In accordance with a preferred embodiment of the present disclosure, the hollow dip tube is made of silicone rubber. Alternatively, the hollow dip tube may be made of a mesh structured material. This particular configuration of the hollow dip tube would enable gas purging from the upper part of the internal space while creating a pathway for the fluid liquid material from the bottom part to the upper part of the internal space, towards the outlet port of the flexible container.

[0056] To ensure correct and safe use, the flexible container may comprise an identification tag. In some further preferred embodiments, the identification tag is a radio-frequency identification (RFID) tag.

[0057] In a further aspect, the disclosure provides a flexible container for simultaneously holding an amount of fluid material and an amount of gas, the container comprising an internal space for holding the fluid material and the gas, the internal space being defined by a flexible front wall and a flexible back wall which are hermetically assembled together by means of a sealed edge substantially surrounding the internal space, and at least one outlet port to enable fluid communication between the internal space and the external environment of the flexible container, wherein the outlet port is arranged at an upper side of the container in its operating orientation such that any fluid material exiting the container through the outlet port flows in an anti-gravity direction through the outlet port. The container is further characterized in that a first flow path for the gas and a second flow path for the fluid material is provided, wherein each flow path has an upstream end in the interior space of the container and a downstream end that is externally located with respect to the interior space. The upstream end of the first flow path is in an upper region of the interior space and the upstream end of the second flow path is in a lower region of the interior space. Optionally, the first and the second flow paths merge between the respective upstream and downstream ends, either within the interior space of the flexible container or externally.

[0058] For example, a hollow dip tube arranged in the internal space and fluidically connected with the outlet port as described above, having one or more holes in the upper region of the interior space such as in proximity to the outlet port, provides a first flow path whose upstream end is provided by the one or more holes through which gas located in the upper region of the interior space can flow into the hollow tube and further through the outlet port At the same time, the hollow dip tube provides a second flow path whose upstream end is the bottom end of the tube through which fluid material located in the lower region of the interior space can flow into the hollow tube and further through the outlet port.

[0059] As a further example, the gas purging means comprising a second outlet port as described above provides a first flow path whose upstream end is provided by the second outlet port through which gas located in the upper region of the interior space can exit the container, whereas the second flow path may be provided by a hollow dip tube whose upstream end is the bottom end of the tube through which fluid material located in the lower region of the interior space can flow into the hollow tube and further through the first outlet port In this case, the hollow tube does not need to have any holes in proximity to the first outlet port

[0060] In a further aspect, the disclosure provides a method for sequentially forcing a gas and subsequently a fluid material to flow out from a flexible container in an anti-gravity direction through at least one outlet port, the method comprising a step of (i) providing a flexible container as described herein-above that is filled with an amount of fluid material and with an amount of gas; (ii) arranging the container to have its operating orientation; and [hi] applying external pressure to the flexible container such as to sequentially force the gas and subsequently the fluid material to flow out from the container. In a further aspect, the disclosure provides for an apparatus adapted for receiving and holding at least one flexible container as described above. In a particular embodiment, the apparatus is adapted for receiving and holding a first and a second flexible container as described above, wherein the first flexible container contains a first substrate and the second flexible container contains a second substrate, the apparatus further comprising means for forcing the substrates to flow from the first and the second flexible container into a processing unit device to process the first and second substrates into a liquid product, wherein said means is adapted for exerting pressure, optionally by means of a pressurized gas, on the external surface of the first and the second flexible container. According to certain embodiments of the present disclosure, the processing unit is a mixing device or a chemical reactor.

[0061] Thus, in accordance with an aspect of the disclosure discussed in detail above, the spacer may be non-hollow, e.g., solid or filled. The non-hollow spacer may be cylindrical or have another elongate shape. Furthermore, the non-hollow spacer may extend substantially along or in parallel to a vertical axis V of the flexible container. The non-hollow spacer can be positioned within the internal space of a flexible container.

[0062] The flexible container for use in an apparatus system for the manufacture of pharmaceutical products, in accordance with the above, comprises an internal space for holding a fluid material, the internal space being defined by a flexible front wall and a flexible back wall that are hermetically assembled together by a sealed edge substantially surrounding the internal space, and at least one outlet port for fluid communication between the internal space and an external environment of the flexible container, wherein the flexible container further comprises the non-hollow spacer positioned withing the internal space. The non-hollow spacer is configured to prevent complete collapse of the flexible container and to maintain an open fluid path to the at least one outlet port.

[0063] In accordance with the disclosure above, the flexible container may further comprise at least one inlet port. Additionally or alternatively, the flexible container may further comprise a further port The further port may be positioned adjacent to the at least one inlet port and / or the at least one outlet port The further port may be used for connection of the non-hollow spacer or the non-hollow spacer may be partially inserted into the further port. The at least one outlet port, at least one inlet port and further port may be located at an upper portion of the flexible container. Additionally or alternatively, the flexible container may comprise a port boat. The port boat is hermetically assembled with the flexible front wall and the flexible back wall to form the internal space of the flexible container. The port boat may be located at an upper portion of the flexible container and may comprise the at least one outlet port, at least one inlet port, and / or further port

[0064] The port boat may be configured to prevent complete collapse of the flexible container similar to the non-hollow spacer. Together, the portboat and the non-hollow spacer maybe configured to form a flow path for fluid material to flow vertically along the spacer and horizontally along the port boat to the at least one outlet port of the flexible container when pressure is exerted on the flexible container.

[0065] Therefore, in accordance with this aspect of the disclosure, by preventing complete collapse of the flexible container via the non-hollow spacer and / or the port boat flow paths may be maintained when the flexible container is subjected to pressure (e.g, positive pressure externally exerted on the flexible container or negative pressure within the flexible container) allowing the prevention of dead zones where fluid material may become trapped due to adherence of the front and back walls of the flexible container to one another.

[0066] The following List A of numbered items are embodiments comprised by the disclosure:

[0067] 1. A flexible container for use in an apparatus system for the manufacture of pharmaceutical products, the flexible container comprising: an internal space for holding a fluid material, the internal space being defined by a flexible front wall and a flexible back wall that are hermetically assembled together by a sealed edge substantially surrounding the internal space, and at least one oufletport for fluid communication between the internal space and an external environment of the flexible container, wherein the flexible container further comprises a non-hollow spacer positioned within the internal space, the non-hollow spacer configured to prevent complete collapse of the flexible container.

[0068] 2. The flexible container according to item 1, wherein the non-hollow spacer is cylindrical. 3. The flexible container according to item 1 or 2, the flexible container further comprising: at least one inlet port.

[0069] 4. The flexible container according to any one of items 1 to 3, the flexible container further comprising: a further port, positioned adjacent to the at least one inlet port and / or the at least one outlet port, and the non-hollow spacer is connected with, or partially inserted into, the further port and extends substantially along or in parallel to a vertical axis V of the flexible container.

[0070] 5. The flexible container according to items 3 or 4, wherein the at least one outlet port, the at least one inlet port, and the further port are located at an upper portion of the flexible container.

[0071] 6. The flexible container according to any one of items 1 to 5, the flexible container further comprising: a port boat located at an upper portion of the flexible container, the port boat comprising the at least one outlet port

[0072] 7. The flexible container according to item 6, wherein the port boat further comprises: the at least one inlet port and the further port

[0073] 8. The flexible container according to item 6 or 7, wherein the port boat is hermetically assembled with the flexible front wall and the flexible back wall to form the internal space of the flexible container.

[0074] 9. The flexible container according to any one of items 6 to 8, wherein the port boat is also configured to prevent complete collapse of the flexible container, wherein the non-hollow spacer and the port boat together are configured to form a flow path for fluid material to flow vertically along the spacer and horizontally along the port boat to the at least one outlet port of the flexible container when pressure is exerted on the flexible container. With regard to the flexible container comprising a spacer, e.g., a non-hollow spacer (also referred to herein as an enclosed spacer), described in detail above, further aspects thereof will be described here in detail.

[0075] In particular, a flexible container is described that is configured to hold a fluid for pressurized dispensing. As discussed above, the fluid may comprise a pharmaceutically active ingredient. For example, the fluid may involve expensive substrates, such as oligo-nucleotides or polynucleotides, proteins, polypeptides, small molecules (such as a low molecular weight organic compounds), vaccine components, etc. Thus, as described in detail above, the flexible container may be used in the manufacture of pharmaceutical products. As the pharmaceutical products may need to be sterile, aseptic, or have a high purity level, conventional pumping techniques where the fluid may be transferred via a pump may be impractical. Instead, the fluid may be transferred from the flexible container by subjecting the flexible container to pressure, e.g., subjecting the flexible container to a positive external pressure and / or subjecting an interior of the flexible container to a negative pressure or a negative pressure differential. However, this type of fluid transfer is also prone to increased dead zones, as described in detail above, in which expensive fluids may not fully or maximally be transferred out of the flexible container due to the collapse of the walls of the flexible container onto themselves when subjected to pressure.

[0076] The flexible container itself comprises a first flexible wall and a second flexible wall as described in detail above (e.g., as a front and back flexible wall). The first and second flexible walls are hermetically sealed together to form an internal space that is configured to hold the fluid. Furthermore, the flexible container comprises at least one outlet port that is configured for outputting the fluid from the internal space, e.g., into an apparatus for processing the fluid. The at least one outlet port may be configured to directly or indirectly couple to the apparatus for processing the fluid.

[0077] The flexible container may further comprise at least one input port configured for inputting fluid into the flexible container, for example, prior to processing, and / or at least one further port As indicated above, the further port may be used for attaching additional structures within or onto the flexible container.

[0078] To prevent dead volumes of the fluid from remaining trapped in the flexible container when it is subjected to pressure, the flexible container further comprises an enclosed spacer. The enclosed spacer may be hollow, solid, and / or filled. The key being that the spacer is enclosed, i.e., there is no internal cavity that is open to the environment of the internal space of the flexible container. Thus, fluid (liquid and / or gas) cannot become entrapped within any internal cavity of the spacer that would then not be transferred out of the flexible container when subjected to pressure. In particular, it is advantageous to reduce surface area of the enclosed spacer that comes into contact with fluid in the flexible container as it offers less surfaces for the fluid to adhere to or geometries in which the fluid (e.g., a liquid comprising pharmaceutically active ingredients and / or gas such as air bubbles) may become entrapped, e.g., internally or on or along the outer surface of the enclosed spacer when the flexible container is subjected to pressure.

[0079] It is also noted here that while the first flexible wall and second flexible wall are made from a flexible material that can elastically deform when subjected to pressure during dispensing, the material should maintain enough rigidity so that when under pressure, the flexible walls do not completely collapse around the enclosed spacer effectively eliminating any fluid path along the enclosed spacer.

[0080] The enclosed spacer may comprise a material that is inert to the fluid in the flexible container. The enclosed spacer may comprise, e.g., be formed from, the same material as those used in the flow path of the fluid from the flexible container into the processing apparatus, such as tubing, e.g., the flexible tube and / or port boat discussed elsewhere herein. For example, the material may comprise silicone, e.g., silicone rubber, and / or an inert polymeric material. As further examples, the material may comprise: CA (cellulose acetate), PTFE (polytetrafluoroethylene), PP (polypropylene), PVDF (polyvinylidene fluoride), glass fiber, and / or a silica. In certain examples where there is no or a low risk associated with adsorption, leachables, or certain substances binding to it, such as polar substances, the enclosed spacer may comprise a hydrophobic material or may have a hydrophobic coating to further prevent the fluid from adhering to the enclosed spacer. Additionally or alternatively, the surface roughness parameters of the enclosed spacer may be selected to reduce adherence of the fluid to the enclosed spacer or to maximize hydrophobic properties of the surface of the enclosed spacer with regard to the fluid. This may be influenced by molding techniques that leave low surface roughness values on the molded product, e.g., here the enclosed spacer, and / or may include subsequent machining steps to adjust the surface roughness of the outer surface of the enclosed spacer.

[0081] In addition, the properties of the surface of the enclosed spacer may also be selected to minimize, prevent, or eliminate the adherence of gases to the enclosed spacer, e.g., air bubbles that may have resulted from the filling process of the fluid into the flexible container. The gas may form bubbles within the flexible container that may then adhere to the enclosed spacer. However, prior to dispensing the fluid from the flexible container, it may be advantageous to purge the gas from the flexible container as it may negatively affect dispensing of the fluid and / or subsequent processing of the fluid if it contains additional gases. Thus, the surface roughness parameters of the outer surface of the enclosed spacer may also be selected to reduce adherence of gases, e.g., as bubbles, such as air bubbles, to the enclosed spacer.

[0082] The enclosed spacer extends from the at least one outlet port into the internal space of the flexible container. In particular, the enclosed spacer is configured to provide a fluid path from the internal space to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer. As such, it is clear that the enclosed spacer does not extend from within the at least one outlet port. Since the enclosed spacer is configured to provide a fluid path to the at least one outlet port, a proximal end of the enclosed spacer, i.e., the end of the enclosed spacer closest to the at least one outlet port is arranged adjacent to the outflow pathway of the at least one outlet port Thus, the proximal end of the enclosed spacer may be arranged to partially cover the at least one outlet port in order to provide the fluid path to the at least one outlet port, e.g., less than 50 percent of the cross-sectional area of the at least one outlet port; may be arranged directly adjacent to the at least one outlet port; or may be arranged spaced away from the at least one outlet port as long as the placement of the enclosed spacer still provides a fluid path to the at least one outlet port, e.g., if the enclosed spacer is arranged too far away from the at least one outlet port, then the first and second flexible walls may be able to collapse onto each other and cut off any fluid path along the enclosed spacer to the at least one outlet port, i.e., the enclosed spacer would no longer provide a fluid path to the at least one outlet port if the proximal end is located too far away.

[0083] The arrangement of the enclosed spacer extending from the at least one outlet port into the internal space of the flexible container may be structured in different ways with or without structural features.

[0084] The enclosed spacer may be free-standing. For example, the enclosed spacer may simply be inserted into the flexible container and the enclosed spacer is not fixed to anything.

[0085] Depending on the geometry of the internal space of the flexible container, the enclosed spacer may be able to freely move within the internal space of the flexible container and may require manual alignment prior to dispensing. Alternatively, the geometry of the internal space of the flexible container may be selected to ensure the positional arrangement of the enclosed spacer within the flexible container and relative to the at least one outlet port, e.g., the internal space of the flexible container may be proportionally cylindrical around the extension of the enclosed spacer.

[0086] Alternatively, the enclosed spacer may be positionally fixed. Either the proximal end or the distal end of the enclosed spacer or both ends of the enclosed spacer may be fixed to maintain the positional arrangement of the enclosed spacer in the flexible container, with particular regard to the relation of the enclosed spacer to the at least one outlet port

[0087] The enclosed spacer may be fixed by hermetically sealing the first and second walls around the enclosed spacer itself, for example with the proximal end of the enclosed spacer protruding outside of the internal space of the flexible container or even outside of the flexible container itself. In a related manner, the hermetical seal may include a mount that the enclosed spacer may be attached to. The mount may be more advantageous than sealing around the enclosed spacer as movement of the enclosed spacer (e.g., during handling, transportation, and / or use) may result in the seal being broken, whereas the mount may be more reliably integrated into the seal and result in less transfer of force to the seal itself from movement of the enclosed spacer. Furthermore, because a free-standing enclosed spacer is not fixed withing the flexible container, movement of the enclosed spacer could potentially lead to a puncture or rupture of the flexible walls.

[0088] Alternatively, the internal space of the flexible container may comprise pockets to fix the enclosed spacer. For example, the internal space of the flexible container may comprise a flap or a strip into which one or both ends of the enclosed spacer may be inserted to ensure the positional arrangement of the enclosed spacer within the flexible container. As another example, the hermetical seal of the flexible container may comprise one or two protrusions for one or both respective ends of the enclosed spacer to slot into; e.g., the longitudinal extension of the enclosed spacer may be greater than the corresponding dimension (such as the height) of the internal space of the flexible container (excluding the corresponding dimension with the protrusion(s)). The pockets may be advantageous as any movement of the enclosed spacer would not transfer forces directly to only the seal and may, therefore, be more robust

[0089] In another aspect, the at least one outlet port may comprise a mount that the enclosed spacer may be attached to or the enclosed spacer may be formed integrally, i.e., monolithically, with the at least one outlet port Here, attaching the enclosed spacer to the at least one outlet port or forming it integrally with the at least one outlet port may be more robust, as discussed above, and also reduce areas where dead volumes of fluid may become entrapped, e.g., in a pocket or protrusion.

[0090] The enclosed spacer may be arranged to extend into the internal space at a specific angle from the at least one outlet port The enclosed spacer may be aligned to be substantially parallel with the at least one outlet port, i.e., a longitudinal axis corresponding to the length or longitudinal extension of the enclosed spacer may be substantially parallel, e.g., within 10 degrees, or, preferably, within 5 degrees, of an axis corresponding to a flow path of fluid through the at least one outlet port, e.g., a central axis of a tube-shaped outlet port. The enclosed spacer may be arranged to extend to an opposing end of the internal space, e.g., the farthest end from the at least one outlet port, from the at least one outlet port, thus, the angle at which the enclosed spacer is arranged is dependent on the geometry of the internal space of the flexible container and where the opposing end is located.

[0091] As discussed above, the enclosed spacer may have various shapes or forms, such as having a cylindrical or polygonal prismatic shape. It is advantageous, however, that the enclosed spacer lacks sharp edges and / or has rounded edges. Because the flexible container is subjected to pressure to dispense the fluid inside, the first and second flexible walls are pressed together and onto the enclosed spacer — with sharp or non-rounded edges, this may result in plastic deformation of the flexible walls, or worse, a rupture or puncture in the flexible container, which may also occur during handling or transportation of the flexible container. Even if the pressure exerted on the flexible container is not enough to result in an instantaneous rupture or puncture, if the flexible container is reused, the edges may result in points of high wear that weaken the flexible walls, plastic deformation of the walls that could also weaken the walls, and / or over time may result in a rupture or puncture in the flexible container.

[0092] The shape or form of the enclosed spacer may also further comprise additional structures to provide additional fluid paths from specified areas of the internal space of the flexible container. For example, the internal space of the flexible container may have a polygonal shape, e.g., a quadrilateral shape, and the flexible walls of the container may also be prone to collapse particularly in corner areas where fluid may become entrapped and build a dead volume. Depending on the orientation of the flexible container during dispensing, fluid may be more prone to becoming trapped in particular corners compared to others. For example, in an upright orientation, the bottom corners at an opposite side of the flexible container from the at least one outlet port may be the most vulnerable to becoming entrapped.

[0093] The distal end of the enclosed spacer may comprise perpendicular extensions that extend into lower corners of the internal space, e.g., in an [inverted) T-shape. The perpendicular extensions may thus be configured to form a fluid path along the perpendicular extension from the corners during pressurized dispensing of the fluid that causes the flexible walls to collapse onto each other and the enclosed spacer. The fluid may then also travel towards the at least one outlet port along the fluid path formed by the enclosed spacer after traveling along the perpendicular extension. The perpendicular extensions may extend completely into the corners or may extend close enough to the corner to prevent collapse of the flexible walls in the corner and to provide the fluid path out of the corners. The perpendicular extensions may also aid enclosed spacer in maintaining its position and relational arrangement in the internal space of the flexible container if the enclosed spacer is free standing.

[0094] In another example, the enclosed spacer may comprise angled extensions extending into the corners of the internal space of the flexible container opposite to the at least one port in an (inverted) Y-shape. The angled extensions (non-perpendicular) may split off the distal end of the enclosed spacer where the length of the enclosed spacer is not commensurate with the corresponding dimension of the internal space of the flexible container. Here, the angled extensions are configured to form a fluid path along the angled extensions from the corners during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer. From the angled extensions, fluid may then flow along the fluid paths formed by the enclosed spacer to the at least one outlet port The angled extensions may extend completely into the corners or may extend close enough to the corner to prevent collapse of the flexible walls in the corner and to provide the fluid path out of the corners. The angled extensions may also aid enclosed spacer in maintaining its position and relational arrangement in the internal space of the flexible container if the enclosed spacer is free standing.

[0095] In another aspect, for example with regard to a quadrilaterally shaped internal space of the flexible container, fluid may be prone to becoming entrapped in all corners of the internal space of the flexible container. Therefore, both the proximal end and the distal end of the enclosed spacer may have perpendicular extensions, e.g., a first perpendicular extension and a second perpendicular extension, that extend into corners of the internal space of the flexible container. The first perpendicular extension may be located at the proximal end of the enclosed spacer and extend into corners of the internal space adjacent to the at least one port and the second perpendicular extension may be located at the distal end of the enclosed spacer and extend into corners of the internal space opposite to the at least one outlet port. The enclosed spacer with the firstand second perpendicular extension may thus form an H- shape rotated 90 degrees or an I-shape (with serifs]. The first perpendicular extension and second perpendicular extension are thereby configured to form a fluid path along the first perpendicular extension and second perpendicular extension from the corners during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer. Here, too, the perpendicular extensions may extend completely into the corners or may extend close enough to the corner to prevent collapse of the flexible walls in the corner and to provide the fluid path out of the corners. The perpendicular extensions may also aid enclosed spacer in maintaining its position and relational arrangement in the internal space of the flexible container if the enclosed spacer is free standing.

[0096] In an additional or alternative aspect, the geometry of the internal space of the flexible container can be shaped to reduce formation of areas of dead zones. For example, in an upright orientation, the internal space of the flexible container may have a shape that converges on a distal end of the enclosed spacer, e.g., in a V-shape or rounded like a U-shape. Thus, corner areas far enough away from the enclosed spacer that the flexible walls may collapse between the corner and the enclosed spacer thereby cutting off a fluid path to the enclosed spacer and / or the at least one outlet port may be eliminated. Additionally or alternatively, any corners of the internal space of the flexible container may be an obtuse angle, or lack 90 degree or acute angled corners that may be more susceptible to collapsing and building dead zones.

[0097] The enclosed spacer and / or any perpendicular or angled extensions of the enclosed spacer may comprise a recess (a longitudinal recess] that extends longitudinally along an outer lateral surface of the enclosed spacer and / or any perpendicular or angled extensions thereof. In other words, the recess may be an indentation in the outer surface along an entire length or substantially the entire length of the enclosed spacer (as opposed to an outer end surface of the enclosed spacer]. The recess may have a curvilinear cross-sectional shape. The recess may provide a fluid path along the enclosed spacer to the at least one outlet port when the flexible walls are collapsed onto all or part of the outer lateral surface of the enclosed spacer. The enclosed spacer may comprise one or more recesses. However, it should be considered that a balance is struck between the number of recesses, the cross-sectional area of the recesses, the desired flow rate along the fluid path(s) of the enclosed spacer, the flexibility of the walls of the flexible container, and the potential for dead volume of fluid being entrapped in the one or more recesses of the enclosed spacer. For example, with a higher flexibility of the walls of the flexible container, when under pressure, the closer the flexible walls will conform around the geometry of the enclosed spacer. Therefore, all other things being equal, the fluid path may be reduced in cross-section, so the cross-sectional area of the recess may be increased to maintain a particular fluid path cross-sectional area and flow rate.

[0098] In an additional aspect of the one or more recesses, the recesses may be aligned with the geometry and structures of the flexible container to improve fluid flow along the fluid paths formed by the enclosed spacer and one or more recesses thereof. For example, the recess or plurality of recesses may be located in a region of the outer lateral surface of the enclosed spacer that faces or is aligned to where the first and second flexible walls are hermetically sealed together. This alignment may be contrasted with a region on the outer lateral surface of the enclosed spacer that faces a flexible wall. As the flexible wall collapses onto an outer lateral surface of the enclosed spacer, there is no gap therebetween and no fluid path for the fluid to flow along. However, the regions of the outer lateral surface that face or are aligned with the opposing seal, the flexible walls are pressed together leaving a gap with a shape having an area that is similar to a tail-end of a teardrop thus forming the fluid path for fluid to flow along the enclosed spacer. When the recesses are aligned with these gaps as described above, the cross-sectional area of the gaps is increased allowing for greater fluid flow along the fluid paths formed by the enclosed spacer and one or more recesses.

[0099] Put another way, the outer lateral surface may be described as comprising a first region that faces the first flexible wall, a second region that faces the second flexible wall, and a third and fourth region located on opposing sides of the outer lateral surface of the enclosed spacer and respectively located between the first and second regions of the outer lateral surface. For example, going clockwise around the outer lateral surface of the enclosed spacer may go from the first region to the third region to the second region to the fourth region. Therefore, the one or more recesses may be located in the third and / or fourth regions of the outer lateral surface of the enclosed spacer.

[0100] With regard to the perpendicular extension or angled extensions, one or more recesses may be also located on an outer lateral surface thereof that is not in contact with the flexible walls and / or seal when the flexible container is subjected to pressure to also increase the cross- sectional area of gaps formed around the extensions by the seal and / or flexible walls.

[0101] In some aspects similar to the longitudinal recess described above, the enclosed spacer and / or any perpendicular or angled extensions of the enclosed spacer may comprise a transverse recess. While the enclosed spacer may aid in fluid flow in a direction parallel to the enclosed spacer, it may also form dead zones itself as fluid on an opposing side of the enclosed spacer to the at least one outlet port may become entrapped when the flexible walls collapse onto the enclosed spacer as there may be no path for the fluid to traverse the enclosed spacer to get to the at least one outlet port Furthermore, as discussed above, gas may become entrapped on either side of the enclosed spacer within the internal space of the flexible container and may not be able to traverse it to be purged from the flexible container prior to dispensing.

[0102] Therefore, the enclosed spacer may further comprise one or more transverse recesses. The transverse recess may extend perpendicularly (relative to the longitudinal extension of the enclosed spacer] across the outer lateral surface of the enclosed spacer. The transverse recess may be located at a proximal end and / or distal end of the enclosed spacer. For additional purposes of removing gas entrapped in the flexible container, the transverse recess may preferably be located at the proximal end of the enclosed spacer. Thus, in contrast to the longitudinal recesses described above, the transverse recess may be aligned with a region of the outer lateral surface of the enclosed spacer that is facing a flexible wall (e.g., a first and / or second region of the outer lateral surface of the enclosed spacer], thereby forming a fluid path across the enclosed spacer to the at least one outlet port during pressurized dispensing of the fluid that causes the first and second flexible wall to collapse onto each other and the enclosed spacer. Furthermore, the transverse recess may form a fluid path across the enclosed spacer to the at least one inlet and / or outlet port when purging gas from the flexible container.

[0103] Additionally or alternatively, the enclosed spacer may comprise a transverse hole extending perpendicularly (relative to the longitudinal extension of the enclosed spacer] through the enclosed spacer. Similar to the transverse recess above, the transverse hole allows for fluid and / or gas to traverse the enclosed spacer. Therefore, the transverse hole is configured to form a fluid path through the enclosed spacer to the at least one outlet port during pressurized dispensing of the fluid that causes the first and second flexible walls to collapse onto each other and the enclosed spacer. Furthermore, the transverse hole may form a fluid path through the enclosed spacer to the atleastone inletand / or outlet port when purging gas from the flexible container.

[0104] Additionally or alternatively, the enclosed spacer may comprise a plurality of transverse protrusions extending perpendicularly across the outer lateral surface of the enclosed spacer. Thus, rather than subtractive structures to the enclosed spacer, structural features may be added to the enclosed spacer that project from the outer lateral surface that prevent the flexible walls from completely collapsing onto the outer lateral surface of the enclosed spacer and allows for fluid and / or gas to traverse the enclosed spacer. Therefore, the plurality of transverse protrusions are configured to form a fluid path across the enclosed spacer to the at least one outlet port during pressurized dispensing of the fluid that causes the first and second flexible walls to collapse onto each other and the enclosed spacer. Furthermore, the plurality of transverse protrusions may form a fluid path across the enclosed spacer to the at least one inlet and / or outlet port when purging gas from the flexible container.

[0105] In another aspect of the disclosure described in detail above, the flexible container may further comprise a port boat. The port boat may further comprise the at least one inlet port and / or further port. The port boat may have a width, e.g., the dimension between the first and second flexible walls, that substantially corresponds to or is proportionate with the dimensions of the ports, e.g., outlet, inlet, and / or further ports. Alternatively, if any part of the ports extends into the internal space of the flexible container, the width of the port boat may be greater than the dimensions of the ports so that it provides a fluid path along the port boat to the at least one outlet port during pressurized dispensing of the fluid that causes the first and second flexible walls to collapse onto each other and the enclosed spacer. Thus, the width of the port boat must be greater than the dimensions of the ports to allow fluid to flow past the ports even when the flexible walls collapse onto the ports or the width of the port boat prevents collapse of the flexible walls onto the ports.

[0106] The port boat may comprise any suitable, inert material, i.e., inert to the fluid in the flexible container, such as silicone, e.g., silicone rubber and / or an inert polymeric material. The port boat may comprise: CA (cellulose acetate), PTFE (polytetrafluoroethylene), PP (polypropylene), PVDF (polyvinylidene fluoride), glass fiber, and / or a silica.

[0107] The port boat may comprise the enclosed spacer, which may be integrally formed (monolithically) with the port boat or may be attached to the port boat In this aspect, the enclosed spacer and the port boat may comprise the same material, e.g., be formed from the same material. The enclosed spacer may be attached to the further port or the port boat may comprise a mount specifically for the enclosed spacer. The enclosed spacer may be attached to the further port via an adapter that adapts the shape and dimensions of the enclosed spacer to that of the further port

[0108] In order to facilitate transverse fluid or gas movement across the enclosed spacer as discussed above, the width of the port boat may also be greater than the corresponding width (or diameter) of the enclosed spacer. This then forms a fluid path across the enclosed spacer and along the port boat during pressurized dispensing of the fluid that causes the first and second flexible walls to collapse onto each other and the enclosed spacer. In an aspect thereof, the smaller width of the enclosed spacer may be located at a proximal end of the enclosed spacer with the width of the enclosed spacer transitioning to a larger width away from the proximal end. The transition may be stepwise, an angled surface, or a rounded surface.

[0109] The following List B of numbered items are embodiments comprised by the disclosure:

[0110] 10. A flexible container configured to hold a fluid for pressurized dispensing, the flexible container comprising: a first flexible wall and a second flexible wall that are hermetically sealed together to form an internal space configured to hold the fluid; at least one outlet port configured for outputting the fluid from the internal space; and an enclosed spacer extending from the at least one outlet port into the internal space of the flexible container, the enclosed spacer configured to provide a fluid path from the internal space to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

[0111] 11. The flexible container accordingto item 10, wherein the enclosed spacer has a cylindrical shape.

[0112] 12. The flexible container accordingto item 10 or claim 11, wherein the enclosed spacer comprises a recess extending longitudinally along an outer lateral surface of the enclosed spacer.

[0113] 13. The flexible container accordingto item 12, wherein the recess is located in a region of the outer lateral surface facing where the first flexible wall and the second flexible wall are hermetically sealed together. The flexible container according to item 12, wherein the outer lateral surface comprises: a first region facing the first flexible wall, a second region facing the second flexible wall, and a third region and a fourth region on opposing sides of the outer lateral surface and respectively located between the first region and the second region of the outer lateral surface; and the recess is located in the third region or the fourth region of the outer lateral surface of the enclosed spacer. The flexible container accordingto item 10 or item 11, wherein the enclosed spacer comprises a plurality of recesses extending longitudinally along an outer lateral surface of the enclosed spacer. The flexible container accordingto item 15, wherein the plurality of recesses are respectively located in opposing regions of the outer lateral surface facing where the first flexible wall and the second flexible wall are hermetically sealed together. The flexible container accordingto item 15, wherein the outer lateral surface comprises: a first region facing the first flexible wall, a second region facing the second flexible wall, and a third region and a fourth region on opposing sides of the outer lateral surface and respectively located between the first region and the second region of the outer lateral surface; and the plurality of recesses are respectively located in the third region and the fourth region of the outer lateral surface of the enclosed spacer. The flexible container accordingto any one of items 10 to 17, wherein the enclosed spacer further comprises a transverse recess extending perpendicularly across the outer lateral surface of the enclosed spacer, the transverse recess configured to form a fluid path across the enclosed spacer to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer. The flexible container according to any one of items 10 to 18, wherein the enclosed spacer further comprises a transverse hole extending perpendicularly through the enclosed spacer, the transverse hole configured to form a fluid path through the enclosed spacer to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer. The flexible container according to any one of items 10 to 19, wherein the enclosed spacer further comprises a plurality of transverse protrusions extending perpendicularly across the outer lateral surface of the enclosed spacer, the plurality of transverse protrusions configured to form a fluid path across the enclosed spacer to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer. The flexible container accordingto any one of items 10 to 20, wherein a distal end of the enclosed spacer comprises a perpendicular extension extending into corners of the internal space opposite to the at least one outlet port, the enclosed spacer forming a T-shape, and the perpendicular extension configured to form a fluid path along the perpendicular extension from the corners during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer. The flexible container accordingto any one of items 10 to 20, wherein a proximal end of the enclosed spacer comprises a first perpendicular extension extending into corners of the internal space adjacent to the at least one outlet port, and a distal end of the enclosed spacer comprises a second perpendicular extension extending into corners of the internal space opposite to the at least one outlet port, the enclosed spacer forming an H-shape, and the first perpendicular extension and second perpendicular extension configured to form a fluid path along the first perpendicular extension and second perpendicular extension from the corners during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

[0114] 23. The flexible container according to any one of items 10 to 20, wherein the enclosed spacer has angled extensions extending into corners of the internal space opposite to the at least one outlet port, the enclosed spacer forming a Y shape, and the angled extensions configured to form a fluid path along the angled extensions from the corners during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

[0115] 24. The flexible container according to any one of items 10 to 20, wherein the internal space of the flexible container has a shape that converges on a distal end of the enclosed spacer.

[0116] 25. The flexible container according to any one of items 10 to 20, wherein the internal space of the flexible container lacks 90-degree corners.

[0117] 26. The flexible container according to any one of items 10 to 25, the flexible container further comprising: a port boat, the port boat comprising: the at least one outlet port, and the enclosed spacer.

[0118] 27. The flexible container according to item 26, wherein the port boat is configured to provide a fluid path along the port boat to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

[0119] 28. The flexible container according to items 26 or 27, wherein the enclosed spacer is integrally formed with the port boat

[0120] 29. The flexible container accordingto items 26 or 27, wherein the port boat further comprises a further port and the enclosed spacer is inserted into the further port

[0121] 30. The flexible container accordingto item 29, wherein the enclosed spacer is connected to the further port via an adapter.

[0122] 31. The flexible container accordingto any one of items 26 to 30, wherein a width of the enclosed spacer is smaller width than a width of the port boat to form a fluid path across the enclosed spacer and along the port boat during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

[0123] 32. The flexible container accordingto item 31, wherein a region where the width of the enclosed spacer smaller than the width of the port boat is located at a proximal end of the enclosed spacer with the width of the enclosed spacer transitioning to a larger width away from the proximal end.

[0124] 33. The flexible container accordingto any one of items 10 to 32, wherein the enclosed spacer is without sharp edges.

[0125] 34. The flexible container accordingto any one of items 10 to 32, wherein the enclosed spacer has rounded edges.

[0126] 35. The flexible container accordingto any one of items 10 to 34, the flexible container further comprising: at least one inlet port.

[0127] 36. The flexible container accordingto item 35, wherein the port boat further comprises the at least one inlet port

[0128] DETAILED DESCRIPTION OF THE DRAWINGS

[0129] Figure 1 depicts the flexible container [1] in a vertical operating orientation, wherein the fluid content leaves the flexible container (1) through an outlet port [6] in an anti-gravity- direction, i.e., in a direction which is substantially the opposite of (i.e., at an angle of about 180° to) the direction towards which the gravity force would naturally pull the fluid content. However, the skilled person understands that the flexible container (1) can be used in any other operating orientation, in function of the specific characteristics of the apparatus and of the manufacturing process conditions which are applied for a specific purpose. The flexible container (1) further comprises a flexible front wall (3) and a flexible back wall (4), both made of a polymeric material. The flexible front wall (3) and flexible back wall (4) are hermetically assembled together by forming a sealed edge (5) which defines an internal space [2] where a fluid material can be stored. The sealed edge (5) comprises two upper corner regions (5a, 5b) and two lower corner regions (5c, 5 d) such that the flexible container (1) has a substantially rectangular overall shape when it is empty. In Figure 1, the corner regions (5a, 5b, 5c, 5d) are rounded corners. However, the corner regions (5a ,5b, 5c, 5d) may have any other shape, such as a pointed or truncated shape, depending on the particular use and / or on the characteristics of the apparatus where the flexible container (1) may be used. The flexible container (1) further comprises two through-holes (11a, lib) positioned in the upper corner regions (5a, 5b). The two through-holes (11a, 11b) permit the container to be held by, or affixed to, in dedicated sites cavities of an apparatus. The outlet port (6) enables fluid communication between the internal space (2) and the external environment of the flexible container (1), thus allowing to fluidically connect the flexible container (1), through appropriate conduits, to, e.g., a processing unit of an apparatus, such as a mixing device or a reactor. An inlet port (7) is provided to enable a second fluid connection in case, for example, the flexible container (1) has to receive fluid material, prior or during use with an apparatus. Under such circumstances, the flexible container (1) may be put in fluid connection with, e.g., a reservoir or a fluid material container positioned upstream of the flexible container (1) in an apparatus, for filling the flexible container (1) prior to starting processing. The outlet port (6) and the inlet port (7) are each connected to a flexible tube (12) and (13), respectively, in order to enable the connection of the flexible container (1) to upstream / downstream units in an apparatus. The flexible container (1) further comprises a means (8) for preventing collapse of the structure of the flexible container (1). In Figure 1, the means (8), which is positioned within the internal space (2), comprises a spacer (10) extending substantially along the vertical axis V of the flexible container (1) for almost the entire height of the flexible container (1). The spacer (10) is inserted into a port (9) positioned between the oudet port (6) and the inlet port (7), the port (9) being hermetically sealed thus preventing fluid communication between the internal space (2) and the external environment of the flexible container (1). The outlet port (6), the inlet port (7) and port (9) are centrally positioned along the upper side of the sealed edge (5) of the flexible container (1). The outlet port (6), the inlet port (7) and the port (9) may also be configured on a common platform, a so-called port boat, which is then hermetically assembled with the front wall (3) and the back wall (4), so to form the internal space (2). In this embodiment of Figure 1, the spacer is a filled tube extending along the vertical axis V of the flexible container (1) and its vertical symmetry axis. In Figure 1, the length of the spacer (10) corresponds to about 90% of the height H of the flexible container (1). Other lengths of the spacer, such as about 80%, about 70%, about 60%, about 50% or less of the height H of the flexible container (1), are also possible and may constitute other aspects within the scope of the present disclosure.

[0130] The spacer (10) within the internal space (2) prevents the structure of the flexible container (1) from complete collapse when the flexible container (1) has been almost totally emptied, for example, after applying pressure on the external sides of its front and back walls (3, 4). As mentioned above, "complete collapse” means, in accordance with the present disclosure, that the front and back walls (3, 4) of the flexible container adhere, at least partially to each other, for example, due to applying external pressure thereon, or by creating vacuum in the internal space (2), when almost no fluid material is present within the internal space (2). Under such circumstances, part of the residual fluid material, particularly in the lower part of the internal space (2) may remain entrapped in so-called "dead zones” and can no longer leave the internal space (2) through the outlet port (6). In accordance with the present disclosure, the spacer (10) prevents adhesion of the front wall (3) with the backwall (4) and creates a pathway along its length towards the outlet port (6), the flexible tube (12) and then outside of the internal space (2). Residual entrapped product quantities within the internal space (2) are therefore reduced or even completely avoided.

[0131] Figure 2 depicts a frontal view of another aspect in accordance with the present disclosure. The flexible container (20) is substantially the same as the flexible container (1) of the Figure 1, except that the means (8) for preventing the collapse of the flexible container (20) are in the form of a membrane (21). The membrane, which in Figure 2 has a rectangular shape, is positioned within the internal space (2). It is inserted between the front wall (3) and the back wall (4) before hermetically assembling them, so as to form the flexible container (20). The presence of the membrane prevents the front wall (3) and the back wall (4) from adhering to each other and, accordingly, it guarantees a fluid passage along its surface. The material of the membrane has to be inert towards the fluid material which the flexible container has to hold. Preferred materials in accordance with the present disclosure are CA (cellulose acetate), PTFE (polytetrafluoroethylene), PP (polypropylene), PVDF (polyvinylidene fluoride), glass fiber, or a silica membrane. The thickness of the membrane may vary between 0.1 and 1 cm, depending on its composition and to which extent the membrane is compressed when applying external pressure. The porosity of the membrane likewise plays a role. The thinner the membrane in the compressed status is, that is when external pressure is applied, the larger its pores have to be in order to allow sufficient flow of the residual fluid material through an outletport (23) towards the external environment of the flexible container (20) for further processing within an apparatus. An inlet port (22) is also provided to enable a second fluid connection in case, for example, the flexible container (1) has to receive fluid material, prior or during use with an apparatus.

[0132] The flexible container (20) depicted in Figure 2 does not require the presence of a third port as in Figure 1 since the membrane is self-sustained within the internal space (2) of the flexible container (20).

[0133] Figure 3 depicts a frontal view of a third aspect of the present disclosure, wherein the flexible container (30) comprises a first outlet port (31), a second outlet port (32) and a flexible tube (33) in fluid connection with the first outlet port (31). The flexible container (30) further comprises a dip hollow tube (35) in fluid connection with the first outlet port (31) and the flexible tube (33) and extending substantially along the vertical axis V of the flexible container (30). The dip hollow tube (35) enables capturing the fluid material residues from the lower part of the internal space (2) and, accordingly, it is possible to fully remove the fluid material from the flexible container (30). The flexible container (30) depicted in Figure 3, however, requires means (34) for gas purging (e.g., air) which remains at the upper part of the internal space (2) and which cannot be expelled though the dip hollow tube (35) which is in the liquid, in the lower part of the internal space (2). The means (34) for gas purging comprises a flexible tube (36) which is in fluid connection with the flexible tube (33) through a tube connecting part (37). The connecting part (37) may be for example a Y- or a T-piece, wherein the Y- or T-piece is arranged for fluidically connecting the flexible tube (33), and therefore the first outlet port (31), with the flexible tube (36), and therefore the second outlet port (32) and the dip hollow tube (35). With such a configuration, when the fluid (liquid) material is urged out of the flexible container (30) through the dip hollow tube (35), the first outlet port (31) and the flexible tube (33), the gas present in the upper part of the internal space (2) can escape the flexible container (30) through the second outlet port (32) and the flexible tube (36) and join the fluid (liquid) material through the tube connecting part (37) for further processing, e.g., in an appropriate processing unit of an apparatus. An inlet port (38) is provided to enable a second fluid connection in case, for example, the flexible container (30) has to receive fluid material, prior or during use with an apparatus.

[0134] Figure 4 depicts a frontal view of a fourth aspect of the present disclosure, which is substantially similar to that of Figure 3 with the exception that the flexible container (40) comprises a faceport (41) instead of a dip hollow tube as previously presented in Figure 3. The faceport (41), which in Figure 4 is positioned in the middle (or lower) part of the internal space (2), functions as the outlet port for the fluid material and it is, in this case, directly in fluid connection with an externally arranged flexible tube (42) for conducting the fluid material to e.g. a further processing unit of an apparatus. The flexible container (40) of Figure 4 comprises a further outlet port (43), for gas purging as described with respect to Figure 3, and an inlet port (44).

[0135] Figure 5 depicts a frontal view of a fifth aspect of the present disclosure, which is substantially the same as that of Figure 3. The flexible container (50) comprises a dip hollow tube (52) in fluid connection with a first outlet port (54) and a flexible tube (56). It further comprises a sterile filter (51) assembled on a second outlet port (55), instead of the means for gas purging described under Figure 3. Accordingly, the air can leave the flexible container (50) through the sterile filter (51) which is detachable with an aseptic disconnector (not shown). In this context, an aseptic disconnector means a readily disconnectable transfer conduit or conduit segment or another conduit having the same or a similar functionality. The aseptic disconnector facilitates the quick removal of the sterile filter (51) product while minimizing the risk of microbiological contamination. An inlet port (53) is provided to enable a second fluid connection in case, for example, the flexible container (50) has to receive fluid material, prior or during use with an apparatus.

[0136] Figure 6 depicts the frontal view of a sixth aspect of the present disclosure, which is substantially the same as that of Figure 3 with the exception that the flexible container (60) comprises a dip hollow tube (61), in fluid connection with an outlet (63) and a flexible tube (64), and having one or more holes (62) (not explicitly shown) at its upper side, that is the side adjacent to an outlet port (63). With such a configuration, the gas which is in the upper part of the internal space (2) may be purged through the one or more holes (62) by joining the fluid (liquid) product coming from the lower part of the internal space (2) through the dip hollow tube (61) and directed through the outlet port (63) and the flexible tube (64), for further processing, e.g., in an appropriate processing unit of an apparatus. A second outlet port is accordingly not necessary. An inlet port (65) is provided to enable a second fluid connection in case, for example, the flexible container (60) has to receive fluid material, prior or during use with an apparatus.

[0137] The following List C of numbered items are embodiments comprised by the disclosure:

[0138] 1. A flexible container (1, 20, 30, 40, 50, 60) suitable for use in an apparatus system for the manufacture of pharmaceutical products, comprising an internal space (2) for holding a fluid material, the internal space (2) being defined by a flexible front wall (3) and a flexible back wall (4) which are hermetically assembled together by means of a sealed edge (5) substantially surrounding the internal space (2), at least one outlet port (6, 23, 31, 43, 54, 63) to enable fluid communication between the internal space (2) and the external environment of the flexible container (1, 20, 30, 40, 50, 60), characterized in thatthe flexible container (1, 20, 30, 40, 50, 60) further comprises a means (8) positioned within the internal space (2) for preventing complete collapse of the flexible container (1, 20, 30, 40, 50, 60).

[0139] 2. The flexible container (1, 20, 30, 40, 50, 60) accordingto item 1, further comprising at least one inlet port (7, 22, 38, 44, 53, 65).

[0140] 3. The flexible container (1) according to item 1 or 2, wherein the means (8) comprises a further port (9), positioned adjacently to the at least one inlet port (7) and / or the at least one outlet port (6), and a spacer (10) connected with, or partially inserted into the further port (9) and extending substantially along or in parallel to a vertical axis V of the flexible container (1).

[0141] 4. The flexible container (1) accordingto item 3, wherein the spacer (10) is a tube.

[0142] 5. The flexible container (20) accordingto item 1 or 2, wherein the means (8) comprises a membrane (21) positioned between the flexible front wall (3) and the flexible back wall (4).

[0143] 6. The flexible container (30, 50) accordingto item 1 or 2, comprising a first outlet port (31, 54) and a second outletport (32, 55), a flexible tube (33, 56) in fluid connection with the first outlet port (31, 54), and a means (34, 51) for gas purging in fluid connection with the second outlet port (32, 55,). The flexible container (30, 50) according to item 6, wherein the means (8) comprises a dip hollow tube (35, 52) in fluid connection with the first outlet port (31, 54) and the flexible tube (33, 56) and extending substantially along or in parallel to a vertical axis V of the flexible container (30, 50). The flexible container (40) according to item 1 or 2, wherein the means (8) comprises a faceport (41) in fluid connection with the first flexible tube (42), the faceport (41) being positioned in the internal space (2) in its middle part (2b) or in its half-part (2a) distal to the at least one outlet port (43). The flexible container (30) according to item 6 or 7, wherein the means (34) for gas purging comprises a flexible tube (36) which is in fluid connection with the flexible tube (33) through a tube connecting part (37). The flexible container (50) according to any item 6, 7 or 8, wherein the means for gas purging comprises a sterile filter (51) detachable with an aseptic disconnector. The flexible container (60) according to item 1 or 2, wherein the means (8) comprises a dip hollow tube (61) in fluid connection with the at least one outlet port (63) and the flexible tube (64) and extending substantially along or in parallel to a vertical axis V of the flexible container (60), wherein the hollow dip tube (61) further comprises one or more holes (62) enabling fluid connection between the internal space (2) and the internal part of the dip hollow tube (61), the one or more holes (62) being positioned towards the extremity of the dip hollow tube (61) which is adjacent to the at least one outlet port (63). The flexible container (30, 50, 60) accordingto any item 7, 9, 10 and 11, wherein the dip hollow tube (35, 52, 61) is made of silicone rubber. The flexible container (30, 50, 60) accordingto any item 7, 9, 10 or 11, wherein the dip hollow tube (35, 52, 61) is essentially made of a mesh structured material. The flexible container (1, 20, 30, 40, 50, 60) accordingto any item 2 to 13, wherein the at least one outlet port (6, 23, 31, 43, 54, 63) and the at least one inlet port (7, 22, 38, 44, 53, 65) are assembled on a port boat. An apparatus adapted for receiving and holding a first and a second flexible container as claimed in one of the items 1 to 14, wherein the first flexible container contains a first substrate and the second flexible container contains a second substrate, the apparatus further comprising means for forcing the substrates to flow from the first and the second flexible substrate container into a processing unit device, optionally a mixing device or a chemical reactor, to process the first and second substrates into a liquid product, wherein said means is adapted for exerting pressure, optionally by means of a pressurized gas, on the first and on the second flexible substrate container.

[0144] Figures 7A and 7B depict flexible container (100). Flexible container (100) may be configured to hold a fluid for pressurized dispensing as described above. Flexible container (100) comprises a first flexible wall (130) and a second flexible wall (140) that are hermetically sealed together via seal (150) to form an internal space (120) configured to hold the fluid. At least one outlet port (160) is configured for outputting the fluid from the internal space (120). Flexible container (100) further comprises an enclosed spacer (110) extending from at least one outlet port (160) into internal space (120) of flexible container (100). The enclosed spacer (110) is configured to provide a fluid path (119) from the internal space (120) to the atleast one outlet port (160) during pressurized dispensing of the fluid that causes the first flexible wall (130) and the second flexible wall (140) to collapse onto each other and the enclosed spacer (110). As depicted in Figure 7B, the cross-sectional shape of enclosed spacer (110) may be cylindrical.

[0145] Figures 8A to 8D depict various aspects of recess (111) of enclosed spacer (110). As shown in Figure 8A, enclosed spacer (110) may comprise a recess extending longitudinally along an outer later surface of enclosed spacer (110). Figures 8B, 8C, and 8D show various cross- sectional shapes of enclosed spacer (110) with one or more recesses (111). For example. Figure 8B shows a single recess (111), Figure 8C shows two recesses (111) on opposing sides of the outer lateral surface of enclosed spacer (110), and Figure 8D shows four recesses (111) arranged along the outer lateral surface of enclosed spacer (110) to form an X-shaped cross- sectional shape. As may be noted here, the transition from recess (111) to the outer lateral surface of enclosed spacer (110) may also lack sharp edges or have rounded edges, as discussed in detail above.

[0146] As depicted in Figure 9, the one or more recesses (111) may be oriented with respect to the geometry and shape of the flexible container (100). As may be seen here, the recesses (111) are located in regions of the outer lateral surface of the enclosed spacer (110) facing where the firstflexible wall (130) and the second flexible wall (140) are hermetically sealed together at seal (150). Put another way as described above, the outer lateral surface of enclosed spacer (110) comprises first region (135) facing the first flexible wall (130), second region (145) facing the second flexible wall (140) and a third and fourth region (155) on opposing sides of the outer lateral surface and respectively located between first region (135) and second region (145). Recesses (111) are located in the third and fourth regions (155) of the lateral surface of enclosed spacer (110). As may also be seen here, in comparison to Figure 7B, the cross-sectional area of fluid path (119) is enlarged due to alignment of recesses (111) allowing greater fluid flow along the fluid path (119). Furthermore, as discussed above, a wall with a higher flexibility may conform more closely to the geometry of the enclosed spacer, and the recesses (111) may therefore allow use of a material for the flexible walls with a comparatively higher flexibility by being able maintain a particular cross- sectional area for the fluid path (119).

[0147] Figures 10A, 10B, and 10C depict aspects of the disclosure allowing fluid and / or gas to traverse enclosed spacer (110).

[0148] As discussed above, enclosed spacer (110) may comprise a transverse recess (112) extending perpendicularly across the outer lateral surface of enclosed spacer (110) as shown in Figure 10A. The transverse recess (112) is configured to form a fluid path across enclosed spacer (110) to the at least one outlet port (160) during pressurized dispensing of the fluid that causes the first flexible wall (130) and the second flexible wall (140) to collapse onto each other and enclosed spacer (110).

[0149] Figure 10B shows transverse hole (113) extending perpendicularly through enclosed spacer (110) as described above. Transverse hole (113) is configured to form a fluid path through enclosed spacer (110) to the at least one outlet port (160) during pressurized dispensing of the fluid that causes the first flexible wall (130) and the second flexible wall (140) to collapse onto each other and the enclosed spacer (110).

[0150] In Figure 10C, a plurality of transverse protrusions (114) are shown extending perpendicularly across the outer lateral surface of the enclosed spacer (110). The plurality of transverse protrusions (114) are configured to form a fluid path through enclosed spacer (110) to the at least one outlet port (160) during pressurized dispensing of the fluid that causes the first flexible wall (130) and the second flexible wall (140) to collapse onto each other and the enclosed spacer (110).

[0151] Figures 11A, 11B, and 11C depict enclosed spacer (110) with various perpendicular or angled extensions.

[0152] In Figure 11A, the distal end of enclosed spacer (110) comprises perpendicular extension (115) extending into corners of internal space (120) opposite to the at least one outlet port ( 160]. The enclosed spacer

[0110] with perpendicular extension (115) forms an (inverted] T- shape with perpendicular extension (115) configured to form a fluid path along perpendicular extension (115) from the corners during pressurized dispensing of the fluid that causes the first flexible wall (130) and the second flexible wall (140) to collapse onto each other and the enclosed spacer (110).

[0153] As shown in Figure 11B, the proximal end of enclosed spacer (110) comprises first perpendicular extension (117) extending into corners ofinternal space (120) adjacent to the at least one outlet port (160) and the distal end of enclosed spacer (110) comprises a second perpendicular extension (116) extending into corners of internal space (120) opposite to the at least one outlet port (160). Enclosed spacer (110] with first perpendicular extension (117] and second perpendicular extension (116) forms a (rotated) H-shape or an I-shape (with serifs). First perpendicular extension (117) and second perpendicular extension (116) are configured to form a fluid path along first perpendicular extension (117) and second perpendicular extension (116) from the corners during pressurized dispensing of the fluid that causes first flexible wall (130) and second flexible wall (140) to collapse onto each other and the enclosed spacer (110).

[0154] Figure 11C shows enclosed spacer (110) comprising angled extensions (118) extending into corners ofinternal space (120) opposite to the at least one outlet port (160). The angled extensions (118) with enclosed spacer (110) form an (inverted) Y-shape. Angled extensions (118] are configured to form a fluid path along the angled extensions (118) from the corners during pressurized dispensing of the fluid that causes first flexible wall (130) and second flexible wall (140) to collapse onto each other and the enclosed spacer (110).

[0155] Figures 12A and 128 depict various forms of internal space (120) of flexible container (100). As shown in Figure 12A, internal space (120) of flexible container (100) has a shape that converges on a distal end of enclosed spacer (110). As discussed above, this shape may eliminate areas where first flexible wall (130) and second flexible wall

[0140] collapse onto each other blocking fluid paths from corners to enclosed spacer (110). In another form, Figure 128 shows internal space (120) of flexible container (100) with only obtuse angled corners (190). Corners (190) may lack right-angled corners or acute-angled corners to prevent dead zones from forming in corners (190) ensuring that even when subjected to pressure during dispensing, dead zones in corners (190) are eliminated or reduced.

[0156] It is noted that while enclosed spacer (110) is exemplarily shown in an adjacent manner to at least one outlet port (160) in the preceding figures, it is noted that the drawings are not intended to limit arrangement and / or positional relationship of enclosed spacer (110) to other features, nor to particularly limit if enclosed spacer (110) is free standing or fixed in the various aspects discussed above.

[0157] Figures 13A and 13B depict flexible container (100) comprising port boat (200). Figure 13A shows port boat (200) may comprise at least one outlet port (160) and at least one inlet port (170). Enclosed spacer (110) may also be part of port boat (200), e.g., fixed to port boat (200) or integrally formed (monolithically) with port boat (200). As shown in Figure 13B, port boat (200) further comprises further port (180). Enclosed spacer (110) may be directed inserted into further port (180) or indirectly inserted into further port (180) via adapter (210).

[0158] As discussed above, port boat (200) may also be configured to provide a fluid path along port boat (200) to the atleast one outlet port (160) during pressurized dispensing of the fluid that causes first flexible wall (130) and second flexible wall (140) to collapse onto each other and enclosed spacer (110).

[0159] In an aspect thereof, Figures 14A and 14B show respective exemplary dimensions of enclosed spacer (110) and port boat (200). As shown in cross-sectional view of port boat (200) in Figure 14A, a width (D) of enclosed spacer (110) is smaller than a width (W) of port boat (200) to form a fluid path across enclosed spacer (110) and along port boat (200) during pressurized dispensing of the fluid that causes first flexible wall (130) and second flexible wall (140) to collapse onto each other and enclosed spacer (110). In Figure 14B, another cross-sectional view of port boat (200) is shown with a region where the width (DI) of enclosed spacer (110) is smaller than the width (W) of port boat (200) is located at a proximal end of enclosed spacer (110) with the width of enclosed spacer (110) transitioning to a larger width (D2) away from the proximal end.

[0160] In the above figures, which are not drawn to scale, repetitive description or features are omitted to highlight aspects being depicted in the figures and is not intended to show specific aspects of the disclosure are not combinable with one another or are not applicable to a specific depiction. The figures are merely exemplary depictions of various aspects of the disclosure. A number of figures show a coordinate system, which includes an x-axis (also corresponding to the v-axis in Figures 1-6), y-axis, and z-axis; the axis not shown is orthogonal to the face of the image, i.e., extending out of and into the page. LIST OF REFERENCE NUMBERS

[0161] 1 Flexible container

[0162] 2 Internal space

[0163] 2a Internal space part distal to the at least one outlet port

[0164] 2b Middle part of the internal space

[0165] 3 Flexible front wall

[0166] 4 Flexible back wall

[0167] 5 Sealed edge

[0168] 5a, 5b Upper corner regions

[0169] 5c, 5d Lower corner regions

[0170] 6 Outlet port

[0171] 7 Inlet port

[0172] 8 Means for preventing collapse of the flexible container 1)

[0173] 9 port

[0174] 10 spacer

[0175] 11a, lib Through holes

[0176] 12 Flexible tube

[0177] 13 Flexible tube

[0178] 20 Flexible container

[0179] 21 Membrane

[0180] 22 Inlet port

[0181] 23 Outlet port

[0182] 30 Flexible container

[0183] 31 First outlet port

[0184] 32 Second outlet port

[0185] 33 Flexible tube

[0186] 34 Means for gas purging

[0187] 35 Dip hollow tube

[0188] 36 Flexible tube

[0189] 37 Tube connecting part

[0190] 38 Inlet port

[0191] 40 Flexible container

[0192] 41 Faceport

[0193] 42 Flexible tube Outlet port

[0194] Inlet port

[0195] Flexible container

[0196] Sterile filter

[0197] Dip hollow tube

[0198] Inlet port

[0199] First outlet port

[0200] Second outlet port

[0201] Flexible tube

[0202] Flexible container

[0203] Dip hollow tube

[0204] Holes

[0205] First outlet port

[0206] Flexible tube

[0207] Inlet port

[0208] Flexible container

[0209] Enclosed spacer

[0210] One or more recesses

[0211] One or more transverse recesses

[0212] Transverse hole

[0213] Plurality of transverse protrusions

[0214] Perpendicular extension

[0215] Second perpendicular extension

[0216] First perpendicular extension

[0217] Angled Extension

[0218] Fluid path

[0219] Internal space

[0220] First flexible wall

[0221] First region

[0222] Second flexible wall Second region

[0223] Seal

[0224] Third and / or fourth region

[0225] At least one outlet port

[0226] At least one inlet port

[0227] Further port

[0228] Corner

[0229] Port boat

[0230] Adapter

Claims

Claims1. A flexible container for use in an apparatus system for the manufacture of pharmaceutical products, the flexible container comprising: an internal space for holding a fluid material, the internal space being defined by a flexible front wall and a flexible back wall that are hermetically assembled together by a sealed edge substantially surrounding the internal space, and at least one outlet port for fluid communication between the internal space and an external environment of the flexible container, wherein the flexible container further comprises a non-hollow spacer positioned within the internal space, the non-hollow spacer configured to prevent complete collapse of the flexible container.

2. The flexible container according to claim 1, wherein the non-hollow spacer is cylindrical.

3. The flexible container according to claim 1 or 2, the flexible container further comprising: at least one inlet port.

4. The flexible container according to any one of claims 1 to 3, the flexible container further comprising: a further port, positioned adjacent to the at least one inlet port and / or the at least one outlet port, and the non-hollow spacer is connected with, or partially inserted into, the further port and extends substantially along or in parallel to a vertical axis V of the flexible container.

5. The flexible container according to claims 3 or 4, wherein the at least one outlet port, the at least one inlet port, and the further port are located at an upper portion of the flexible container.

6. The flexible container according to any one of claims 1 to 5, the flexible container further comprising:a port boat located at an upper portion of the flexible container, the port boat comprising the at least one outlet port7. The flexible container according to claim 6, wherein the port boat further comprises: the at least one inlet port and the further port8. The flexible container according to claim 6 or 7, wherein the port boat is hermetically assembled with the flexible front wall and the flexible back wall to form the internal space of the flexible container.

9. The flexible container according to any one of claims 6 to 8, wherein the port boat is also configured to prevent complete collapse of the flexible container, wherein the non-hollow spacer and the port boat together are configured to form a flow path for fluid material to flow vertically along the spacer and horizontally along the port boat to the at least one outlet port of the flexible container when pressure is exerted on the flexible container.

10. A flexible container configured to hold a fluid for pressurized dispensing, the flexible container comprising: a first flexible wall and a second flexible wall that are hermetically sealed together to form an internal space configured to hold the fluid; at least one outlet port configured for outputting the fluid from the internal space; and an enclosed spacer extending from the at least one outlet port into the internal space of the flexible container, the enclosed spacer configured to provide a fluid path from the internal space to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

11. The flexible container according to claim 10, wherein the enclosed spacer has a cylindrical shape.

12. The flexible container according to claim 10 or claim 11, whereinthe enclosed spacer comprises a recess extending longitudinally along an outer lateral surface of the enclosed spacer.

13. The flexible container according to claim 12, wherein the recess is located in a region of the outer lateral surface facing where the first flexible wall and the second flexible wall are hermetically sealed together.

14. The flexible container according to claim 12, wherein the outer lateral surface comprises: a first region facing the first flexible wall, a second region facing the second flexible wall, and a third region and a fourth region on opposing sides of the outer lateral surface and respectively located between the first region and the second region of the outer lateral surface; and the recess is located in the third region or the fourth region of the outer lateral surface of the enclosed spacer.

15. The flexible container according to claim 10 or claim 11, wherein the enclosed spacer comprises a plurality of recesses extending longitudinally along an outer lateral surface of the enclosed spacer.

16. The flexible container according to claim 15, wherein the plurality of recesses are respectively located in opposing regions of the outer lateral surface facing where the first flexible wall and the second flexible wall are hermetically sealed together.

17. The flexible container according to claim 15, wherein the outer lateral surface comprises: a first region facing the first flexible wall, a second region facing the second flexible wall, and a third region and a fourth region on opposing sides of the outer lateral surface and respectively located between the first region and the second region of the outer lateral surface; and the plurality of recesses are respectively located in the third region and the fourth region of the outer lateral surface of the enclosed spacer.

18. The flexible container according to any one of claims 10 to 17, wherein the enclosed spacer further comprises a transverse recess extending perpendicularly across the outer lateral surface of the enclosed spacer, the transverse recess configured to form a fluid path across the enclosed spacer to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

19. The flexible container according to any one of claims 10 to 18, wherein the enclosed spacer further comprises a transverse hole extending perpendicularly through the enclosed spacer, the transverse hole configured to form a fluid path through the enclosed spacer to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

20. The flexible container according to any one of claims 10 to 19, wherein the enclosed spacer further comprises a plurality of transverse protrusions extending perpendicularly across the outer lateral surface of the enclosed spacer, the plurality of transverse protrusions configured to form a fluid path across the enclosed spacer to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

21. The flexible container according to any one of claims 10 to 20, wherein a distal end of the enclosed spacer comprises a perpendicular extension extending into corners of the internal space opposite to the at least one outlet port, the enclosed spacer forming a T-shape, and the perpendicular extension configured to form a fluid path along the perpendicular extension from the corners during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

22. The flexible container according to any one of claims 10 to 20, whereina proximal end of the enclosed spacer comprises a first perpendicular extension extending into corners of the internal space adjacent to the at least one outlet port, and a distal end of the enclosed spacer comprises a second perpendicular extension extending into corners of the internal space opposite to the at least one outlet port, the enclosed spacer forming an H-shape, and the first perpendicular extension and second perpendicular extension configured to form a fluid path along the first perpendicular extension and second perpendicular extension from the corners during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

23. The flexible container according to any one of claims 10 to 20, wherein the enclosed spacer has angled extensions extending into corners of the internal space opposite to the at least one outlet port, the enclosed spacer forming a Y shape, and the angled extensions configured to form a fluid path along the angled extensions from the corners during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

24. The flexible container according to any one of claims 10 to 20, wherein the internal space of the flexible container has a shape that converges on a distal end of the enclosed spacer.

25. The flexible container according to any one of claims 10 to 20, wherein the internal space of the flexible container lacks 90-degree corners.

26. The flexible container according to any one of claims 10 to 25, the flexible container further comprising: a port boat, the port boat comprising: the at least one outlet port, and the enclosed spacer.

27. The flexible container according to claim 26, wherein the port boat is configured to provide a fluid path along the port boat to the at least one outlet port during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

28. The flexible container according to claims 26 or 27, wherein the enclosed spacer is integrally formed with the port boat29. The flexible container according to claims 26 or 27, wherein the port boat further comprises a further port and the enclosed spacer is inserted into the further port30. The flexible container according to claim 29, wherein the enclosed spacer is connected to the further port via an adapter.

31. The flexible container according to any one of claims 26 to 30, wherein a width of the enclosed spacer is smaller than a width of the port boat to form a fluid path across the enclosed spacer and along the port boat during pressurized dispensing of the fluid that causes the first flexible wall and the second flexible wall to collapse onto each other and the enclosed spacer.

32. The flexible container according to claim 31, wherein a region where the width of the enclosed spacer is smaller than the width of the port boat is located at a proximal end of the enclosed spacer with the width of the enclosed spacer transitioning to a larger width away from the proximal end.

33. The flexible container according to any one of claims 10 to 32, wherein the enclosed spacer is without sharp edges.

34. The flexible container according to any one of claims 10 to 32, wherein the enclosed spacer has rounded edges.

35. The flexible container according to any one of claims 10 to 34, the flexible container further comprising:at least one inlet port.

36. The flexible container according to claim 35, wherein the port boat further comprises the at least one inlet port37. An apparatus for manufacturing a pharmaceutical product, the apparatus configured to receive one or more flexible containers according to any one of claims 10 to 36 and subject the one or more flexible containers to pressure to dispense fluid from the one or more flexible containers for processing by the apparatus.

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