Storage / containment unit for flexible pouches filled with biopharmaceutical fluids and method of assembling a freeze / thaw containment system using a protective body part

Abstract

A freeze / thaw containment system is provided, which includes a protective body and a flexible pouch protected by two plates of the protective body. The two plates are attached together at a peripheral margin to form a rectangular protective body. The peripheral margin is mounted within a support part of a stationary frame, and a sliding positioning member is fixed to the peripheral margin, allowing the peripheral margin to be guided and displaced inward during filling of the pouch, while the protective body extends generally planarly and clamps and restrains the pouch when the pouch is empty. This manner of holding and sustaining the protective body allows for gradual conformational changes of the protective body due to changes in the volume of the pouch when it is filled with a biopharmaceutical product, while facilitating reverse displacement of the peripheral margin during drainage operations.

Description

[Technical Field]

[0001] The present invention relates generally to the protection of flexible pouches specially designed to store biopharmaceutical fluids, and more broadly to systems for storing biopharmaceutical fluids. The present invention also relates to methods for manufacturing / assembling such systems adapted to freeze and thaw biopharmaceutical fluids therein. Biopharmaceutical fluids refer to fluids derived from biotechnology, such as culture media, cell culture media, buffer solutions, artificial nutritional fluids, blood fractions, blood-derived components, or pharmaceutical fluids, or more broadly to fluids specifically designed for use in the medical field. It should be understood that fluids can become solid or partially solid after freezing (typically at temperatures much lower than 0° C.). [Background technology]

[0002] It is known to use flexible pouches to store biopharmaceutical fluids. Flexible pouches can withstand low mechanical stress without damage, thus reducing the risk of leakage. Moreover, flexible pouches are advantageous because they can be folded or stored flat when no biopharmaceutical fluid is present inside. Therefore, flexible pouches occupy a small volume.

[0003] Flexible pouches are generally designed for single use and are designed to store biopharmaceutical fluid volumes between 1 liter and 500 liters.

[0004] However, specifically for shipment of fluid-filled flexible pouches, for example between several plant areas or from the fluid provider to the client that will use it, and also for storage, the flexible pouches must be protected, even though the risk of leakage is small.

[0005] Patent Document 1 discloses a container for flexible pouches. The container includes a lower part and an upper part, which are rigid and joined along a common edge to form a single-piece container. The container has a volume that is much more significant than the volume of the flexible pouches. As a result, the container has a useless volume. Moreover, if the flexible pouch is not maintained in the container by an appropriate positioning means provided therein, it may be shifted within the container, especially during shipping. Therefore, the risk of leakage increases.

[0006] Single-use polymer containers (hereafter referred to as bags or pouches) have been successfully used for the storage of liquid biopharmaceuticals. Currently, bags made from ethylene vinyl acetate (EVA) or low-density polyethylene (LDPE) have been found to be suitable for the storage and shipping of biological bulk at ambient or cryogenic temperatures (2°C to 8°C). However, problems exist for freezing applications with bags as currently constructed. At low temperatures, the physical properties of the plastic material can change sufficiently to introduce brittleness, which can reduce the bag's capacity to absorb external forces (i.e., impact) without fracture. In addition, the volumetric expansion of ice can cause significant mechanical stress, leading to breakage of the bag, ports, tubing, or connectors. It is well known that currently available unprotected bags do not adequately protect frozen products.

[0007] To eliminate the problems associated with bag breakage, Sartorius Stedim Biotech developed the Celsius™ FFT concept (FFT stands for "Flexible Freeze and Thaw"), which combines a flexible pouch with a semi-rigid protective shell whose contribution is predominant in absorbing stresses resulting from processing or handling conditions.

[0008] Patent Document 2 provides a protective body part in which a flexible pouch is sandwiched between two plates of the protective body part with a restraining effect. A freeze / thaw protection system can be obtained by combining such a protective body part with a single-use flexible container wrapped by a protective shell. However, uniform fluid distribution can be difficult because, in a filled state of the flexible container, a significant bulge (large belly) is formed in the middle. Therefore, in a frozen state, the expansion of ice is relatively significant, and more time is required to freeze this large mass in the middle of the pouch's internal volume.

[0009] Patent document 3 discloses a combination of a single-use container (flexible container) and a shell, in which a tufting coupling is provided to divide the cavity of the container into several regions. This is of interest to limit the risk of significant bulging and to prevent the concentration of liquid mass in the middle part of the flexible container. Such a design cannot be widely used, especially because it makes the container design more complex, which increases the cost of the single-use container. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] European Patent Application Publication No. 2322442 [Patent Document 2] US Patent Application Publication No. 2018 / 125757 [Patent Document 3] International Publication No. 2015 / 200218 Brochure [Patent Document 4] International Publication No. 03 / 037082 Brochure Summary of the Invention [Problem to be solved by the invention]

[0011] The object of the present invention is to provide a storage unit to obtain a robust freeze / thaw containment and protection system that is efficient for preparing large quantities of biopharmaceutical materials in flexible pouches of flexible design (typically 2D pouches that expand in the filled state) while maintaining the flexibility of design for the flexible pouches.

[0012] Moreover, it would be of interest to have a storage unit suitable to efficiently accommodate different pouch states (unfilled, filled, for example, above 50 liters or 70 liters) and different temperatures (which, when frozen, cause considerable differences in the volume of the pouch). [Means for solving the problem]

[0013] To this end, an embodiment of the present invention is a system for preparing a biopharmaceutical composition, the system being for use in freezing, storing, and thawing a biopharmaceutical composition contained in a flexible pouch, the system comprising: - a protective body including two plates for protecting the pouch, the protective body including a longitudinal axis and four sides, the four sides including two longitudinal sides extending parallel to the longitudinal axis and two other sides; - an attachment system for fastening two plates, wherein the protective body part includes a peripheral margin extending annularly in a reference plane of the protective body part, the peripheral margin being provided with at least one opening capable of receiving at least one port of the pouch; a plurality of positioning members fixed to or formed on the peripheral margin; a frame extending around a hollow space into which the pouch extends, the frame being provided with two longitudinal support parts distinct from the positioning member; and Including, The frame includes abutment surfaces contained and distributed among the two longitudinal support parts, and a plurality of positioning members connect the peripheral margins to the frame, and the frame includes: - with protective body part; - A pouch sandwiched between two plates that restrain the pouch; has become a sustained supporter of a slider forming a positioning member of the plurality of positioning members is slidably mounted on or in the two longitudinal support parts and is movable between a first position and a second position along a direction transverse to the longitudinal axis; - in a first position, in an unfilled state of the pouch, the slider is pushed outward by the protective body part or maintained away from the abutment surface, such that the slider can be displaced inward (due to a change in conformation of the protective body part); - in a second position, in a filled state of the pouch, the sliders are respectively engaged against one of the abutment surfaces, providing a system.

[0014] Such an arrangement can allow for contraction of the protective body (at / along the protective body reference plane) due to the filling operation, possibly accompanied by an increase in the height of the pouch, while controlling the contraction thanks to the control of the stroke of a slider attached to the peripheral margin. The protective body can include two pieces (forming plates) to constrain the pouch, which is essentially made from two plastic sheets. The system can include a flexible pouch that is initially flat (in the unfilled state) and configured to contain the biopharmaceutical composition in the pouch's expanded state.

[0015] Filling the pouch causes a conformational change in the protective body portion, accompanied by contraction of the protective body portion in the protective body portion reference plane, resulting from the slider passing from the first position to the second position. In an empty or low-fill state (e.g., less than 5%, or less than 1 or 2 kg), the relative rigidity of the protective body portion is sufficient to cause the center of gravity of the fluid mass (in the case of a homogeneous fluid) to be located substantially within the reference plane. Typically, the deformation of the lower plate can be similar or identical to the deformation of the upper plate. It is understood that at high fill levels, the lower plate can be deformed downward with substantially the same amplitude as the upper plate is deformed upward.

[0016] During the filling operation, the slider can be progressively displaced inward toward the abutment surface, the slider being configured to allow controlled contraction of the protective body outer periphery in the protective body reference plane.

[0017] The freeze / thaw containment system allows the peripheral margin to be mounted within a stationary frame thanks to a sliding positioning member (slider), which is typically fixed to the peripheral margin and allows the peripheral margin to be guided and displaced inward during pouch filling. Such displacement occurs while the protective body extends generally planarly and clamps and restrains the pouch in its empty and lightly filled states. This manner of holding and sustaining the protective body allows for gradual conformational changes of the protective body due to changes in the pouch's volume as it is filled with a biopharmaceutical product, while facilitating reverse displacement of the peripheral margin during drainage. The restraining effect near the peripheral margin can be gradually and slightly released by slider displacement, thus improving filling near the pouch edge. Such an arrangement can also be adapted for shrinkage management, for example, by controlling the sliding stroke of the slider. This is of interest to ensure that the protective body remains as flat as possible, for example, to maintain a maximum height / thickness of the covering portion of the protective body of less than 24 cm or 25 cm before or after the frozen state when the pouch is large and when the pouch is adapted to be filled with at least 70 or 75 liters of biopharmaceutical composition.

[0018] Typically, the two longitudinal support parts are rigid and are made, for example, from aluminum or alloy pieces. More generally, the density of the longitudinal parts is less than 1 g / cm 3 It is possible to achieve much higher values (e.g., 2 g / cm 3 Moreover, the tensile strength of the material of the longitudinal support part can be about 120 MPa or more.

[0019] The Young's modulus of the material of the longitudinal support parts is optionally comprised between 60 GPa and 80 GPa, more generally it being understood that the Young's modulus of the longitudinal support parts is such that these parts are stiffer than the plates of the protective body part, which in turn are stiffer than the materials forming the two sheets of the pouch.

[0020] Aluminum is well suited to low temperature environments. Optionally, the inward deflection of the longitudinal parts (as measured perpendicular to the longitudinal axis) cannot exceed 5 mm for longitudinal support parts made from pieces longer than 1200 mm, such that these longitudinal parts are appreciably rigid (very limited deflection).

[0021] The storage unit formed by the protective body and the filled pouch can be contracted in a controlled manner through a slider (e.g., acting as a stopper) and a rigid part, which can form a C-shaped section frame or any similar section that is open on the inner side. Since the stoppers formed by the sliders are edge-attached at the peripheral margin, they can be easily encapsulated into respective housings delimited by longitudinal support parts. The C-shaped frame can be of interest, especially for adding a gap between the stopper and the abutment surface to allow the slider / stopper to move.

[0022] Typically, the protective body part may have rectangular shaped peripheral sides (i.e., with two parallel long sides and two short sides perpendicular to the long sides). Furthermore, the system may be provided with a slider that moves in one direction, - the one direction defines the X direction with respect to the slider / stop located on the long side of the protective body part; - the one direction defines the Y direction with respect to the slider / stopper located on the short side of the protective body part; Here, X corresponds to the direction of the longitudinal axis X1 and Y corresponds to the transverse direction, both of which are along the protective body reference plane.

[0023] This two-axis freedom of movement will allow the protective body part to contract and expand vertically (i.e., along the Z direction to fill the pouch in the required volume without allowing too much contraction in some intermediate regions), and such a control effect can be obtained by using only sliders located on the long sides of the protective body part, at the peripheral margins, to be effective in limiting the maximum height of the protective body part and in limiting the bulging effect.

[0024] It is understood that the two plates are sufficiently flexible to allow the protective body to have a greater thickness in the central area than in the peripheral areas, relative to the protective body reference plane, the thickness being measured between the lower and upper surfaces along a direction perpendicular to the protective body reference plane.

[0025] According to an embodiment, the flexible pouch is directly sandwiched between two plates that restrain the flexible pouch. The flexible pouch is typically more flexible than the material of the protective body. The restraining effect is of interest for the step of emptying the flexible pouch and is also advantageous for limiting fluid expansion (vertical expansion when the protective body extends generally horizontally so that the protective body reference plane extends substantially horizontally), especially during freezing.

[0026] The two plates are capable of restraining the flexible pouch by means of respective covering portions that extend between two margin portions of the peripheral margin.

[0027] Typically, the protective body part is attached to cover the two main opposite sides of the flexible pouch and acts as an expansion guide element adapted to expand in volume in an expanded state so that the assembly consisting of the protective body part and the flexible pouch covered by it can fill the inner cavity bounded by the two protective parts or the gap bounded between the two protective parts without excessive bulging in the covering part intermediate part, which is provided at equal distances from the front and rear edges of the flexible pouch and separates two other complementary parts of the same longitudinal size as the determined longitudinal size of the intermediate part (the determined size is therefore substantially equal to 1 / 3 of the longitudinal size of the flexible pouch, since the covering part has the same length as the flexible pouch).

[0028] The plates are removably secured to one another by a mounting system, which is (selectively) distributed around the peripheral margins.

[0029] The two opposing margin portions (provided longitudinally at the peripheral margin) are part of the fastening assembly for preventing any shifting movement of position between the two plates when the two plates are fastened to each other at at least two margin portions in a predetermined overlapping configuration to form the protective body portion.

[0030] In two opposite margin portions, protruding parts of the plate are provided, which protrude in a single direction or in two opposite directions. The protruding parts can form first interlocking elements, which are engaged, snap-fastened, fitted, or loosely fitted / received into cavities of the positioning member. Additionally or alternatively, tongues can be provided in the positioning member, which are inserted into hollow portions of the margin portions, which are typically internally bounded by the protruding parts (which are hollow protruding parts).

[0031] The one or more tongues and the one or more cavities of the positioning member may be formed in the same piece, which is either a lower part that is located below the peripheral margin of the protective body part (below the reference plane) or an upper part that is located above the peripheral margin of the protective body part (above the reference plane).

[0032] Optionally, each of the two plates includes embossments or bosses that, in the assembled state of the plates (to form the protective body), define several protective body embossments that protrude in a first direction perpendicular to the protective body reference plane, and may be hollow to form corresponding cavities that open in a second direction opposite the first direction. Such embossments or bosses are selectively distributed at the peripheral margin.

[0033] Two groups of boss portions may be provided, with the boss portions of the first group projecting in a first direction, while the boss portions of the second group projecting in a second direction.

[0034] The positioning member may be provided with one or two recesses configured for insertion (preferably, fitted insertion or clipping) of the boss portion of the plate, and may be provided with a tongue for fitted insertion or clipping into a hollow or cavity in the peripheral margin.

[0035] Typically, the positioning member is secured by a bayonet action, by simple pushing in a direction transverse to the protective body reference plane, which may be performed before or after assembling the two plates together.

[0036] Alternatively, several protective body through slots are provided, distributed longitudinally in each of the two opposite margin portions.

[0037] The attachment devices may interact with some of the protective body portion through-slots or may be distributed in alternating locations relative to the protective body portion through-slots.

[0038] Typically, the frame intersects the protective body portion reference plane and extends parallel to the protective body portion reference plane, and the frame is configured to directly or indirectly retain the protective body portion.

[0039] In a variant, one of the four sides is constrained so that the frame comprises three profiles extending parallel to the protective body reference plane.

[0040] According to a particular feature, at least one of the two plates is provided with outwardly projecting ribs for local structuring of the protective body, at least in the peripheral area around the intermediate part of the protective body. The plates may each be provided with one or two panel parts without ribs, externally delimited by ribs having a U-shaped design as observed in elevation (away from the protective body reference plane).

[0041] In various embodiments of the system, one or more of the following arrangements may optionally be relied upon: - The two plates are two distinct pieces each having four edges, each having a planar inner surface (each planar inner surface completely covering one of the two outer surfaces of the pouch in the unfilled state). The two plates may have the same thickness, lower than 2 mm, and each of the two plates may have a density of 1.10 g / cm 3 and is made from a plastic material. The two plates are made from the same plastic material, preferably transparent or translucent. - The protective body portion is made from a freeze-resistant polyester or copolyester material that is not brittle at approximately 25°F or -4°C. - The material of the protective body is PET. - The material of the protective body is TRITAN (i.e., a copolyester compound called TRITAN™, which is a transparent, amorphous thermoplastic material that is typically made by combining three monomers; some formulations of this material contain no additives, while others contain about 10% or less of additives). The protective body material is an amorphous copolyester made by combining the following monomers: dimethyl terephthalate, 2,2,4,4-tetramethyl-1,3-cyclobutanediol, and 1,4-cyclohexanedimethanol. - The protective body part is directly engaged by a positioning element belonging to the mounting device and has a shrinkage profile at the periphery of the protective body part, optionally in the marginal parts, where shrinkage due to the direct engagement of the positioning element engaged in the intermediate region of the protective body part is hardly reduced or is less. The positioning elements are distributed around the covering portion. - each of the positioning members is engaged to extend through one of the two opposing margin portions by extending through at least one cut or recess formed in one of the two margin portions; - the protective body reference plane intersects with four marginal parts, the four marginal parts being distributed in a rectangular shape and in contact with two protective parts of the shell respectively, the four marginal parts being arranged around the covering part, and the two opposite marginal parts being part of this group of four marginal parts. - The positioning member is distinct and separate from the pouch and the plate, and the positioning member is configured to protrude from at least one of the lower surface and the upper surface of the protective body portion at a peripheral margin, respectively. - the protective body portion extends planarly along a protective body portion reference plane in the empty state of the pouch; the two plates are sufficiently flexible to allow the protective body to have a greater thickness in the central area than in the peripheral areas, relative to a protective body reference plane, the thickness being measured between the lower and upper surfaces of the protective body along a direction perpendicular to the protective body reference plane; - The pouch is directly sandwiched between two plates that restrain the pouch. The positioning member is part of the mounting system. The positioning member is provided with one or more insert parts for being removably inserted onto the peripheral margin. - the peripheral margin is of rectangular shape and is provided with a plurality of hollows, the hollows being distributed over two longitudinal margin portions, which are the two longer portions of the peripheral margin; The plurality of hollow portions includes at least one hollow portion within one or two shorter margin portions of the peripheral margin, each shorter margin portion being elongated along the transverse direction. Each of the positioning members fills (and covers) at least one of the cavities provided in the peripheral margin. At least one of the positioning members overlaps a portion of the mounting system. Optionally, the positioning member does not extend beyond the outer periphery (defining the outer periphery) of the protective body portion. The positioning member comprises a lower part and an upper part, respectively, which are two separate pieces configured to clamp the protective body part in the area of the peripheral margin. - The positioning member includes a lower part and an upper part, each of which is two separate pieces configured to clamp the protective body part in a clamping region of the peripheral margin, each clamping region being elongated parallel to the protective body part edge and preferably at least four times longer than the maximum width of the positioning member. - The slider is part of the mounting system. The sliders each support or include an insert piece that is engaged in the protective body part through the thickness of the peripheral margin. the positioning members are distributed at different longitudinal locations along the longitudinal axis; The two longitudinal support parts may cover or overlap two opposite margin portions of the peripheral margin. The peripheral margins can be received in four respective housings of the frame structure, which includes two longitudinal support parts. - the two longitudinal support parts are part of a holding and retaining device, typically constructed as a frame, and the positioning members are each provided with two separate parts (upper and lower parts) that are interlocked so that the protective body part is sandwiched between the two separate parts and so that the protective body part is positioned in the gap bounded by the two separate parts. - the frame comprises profiles, for example with a U-shaped or C-shaped cross section, each of which delimits an internal cavity, and the positioning members are respectively arranged inside one of the respective cavities of the frame, with positioning members selectively movable inward according to a stroke that depends on the clearance provided inside the cavity, and when an abutment surface belonging to a given positioning member abuts an abutment edge or abutment surface contained in the profile (which houses the given positioning member), the positioning member acts as a stop for limiting the expansion of the protective body part. The abutment surface is contained in an abutment member extending transversely to the protective body reference plane (the abutment surface cooperating with a slider movable along the transverse direction). Each of the abutment members is configured to separate a hollow space from a cavity through which at least one of the sliders extends.

[0042] The abutment surface may be formed after forming the storage unit, which may include or consist of a pouch, a protective body portion, and a mounting system with a positioning member.

[0043] When the positioning member is connected to the peripheral margin, the slider is encapsulated into the C-shaped profile of the frame structure / frame (by the protective body edge (which typically involves the entire peripheral margin)) or can be encapsulated in any suitable housing of the frame. The two longitudinal parts can form the two profiles of the frame.

[0044] This encapsulation allows the protective body to be better maintained, optionally at the peripheral margins, while the pouch remains securely protected. In addition, the encapsulation allows for desired management of conformational changes of the storage unit during filling operations and during temperature changes (associated with freezing operations).

[0045] It is understood that filling of the pouch with the biopharmaceutical composition causes expansion along a direction perpendicular to the protective body reference plane, which means contraction of the protective body (in the protective body reference plane) until an abutment configuration (second position for the slider) is reached.

[0046] In some embodiments, the abutment surfaces may be formed as any suitable stop parts distributed among the two longitudinal slide / profile / support parts, which are configured to stop the slider by abutment of a front abutment surface contained or supported by the slider.

[0047] A first longitudinal support part selected from the two longitudinal support parts can define a first housing, and the slider includes a first slider fitted into at least one cavity defined by the first housing.

[0048] Additionally, the two longitudinal support parts may include a second longitudinal support part defining a second housing, and the slider also includes a second slider fitted into at least one cavity defined by the second housing.

[0049] In some options, the slider comprises an elongated piece of molded plastic material having first and second long sides that are substantially parallel (and, when connected to the margin portion, are parallel to the protective body side). The slider, which may have a rectangular shape, has an interlocking means or insert that is located closer to the first side than to the second side, and the slider is connected to the protective body by the interlocking means or insert. Typically, the second side forms an offset contact surface for early contact with the abutment surface when the second side faces the abutment surface.

[0050] The orientation of the elongated pieces is such that the positioning members (typically located in a profile cavity or similar cavity of the frame) are closer or further from the abutment surface in the initial, unfilled state of the flexible pouch. The positioning members with their second side facing the abutment surface will be stopped earlier by the abutment surface during the filling operation. In other words, the same elongated pieces with such asymmetry can serve to form positioning members that can more or less limit the shrinkage of the plate when mounted (and engaged) in / within a longitudinal support part belonging to the frame. Such a higher restriction of shrinkage is preferred in or near the central transverse plane (intermediate region) of the protective body. In some embodiments, the frame is further provided with one or two transverse support parts, which are rigid and separate from the positioning members. Typically, each of the one or two transverse support parts houses an additional slider, which is - forming each of the positioning members among the plurality of positioning members, - being slidably mounted on or in a corresponding transverse support part, respectively, and being movable along the direction of the longitudinal axis.

[0051] The frame has a rectangular shape thanks to the two longitudinal support parts and the transverse support parts, and the peripheral margin is rectangular (corresponding to the rectangular peripheral sides / perimeter). For compactness, abutment surfaces can be provided in areas in an overlapping configuration with respect to the peripheral margin. Such abutment surfaces therefore do not extend radially beyond the outer perimeter of the protective body.

[0052] the frame includes an additional abutment surface contained and distributed between the two transverse support parts, the additional slider being movable between a first position and a second position along the direction of the movable longitudinal axis; - in a first position, in an unfilled state of the pouch, the additional slider is pushed outward by the protective body portion or maintained away from the additional abutment surface, such that the additional slider can be displaced inward due to a conformational change of the protective body portion; In the second position, in the filled state of the pouch, the sliders are respectively engaged against one of the additional abutment surfaces.

[0053] The support parts belong to a holding and sustaining assembly, which allows the two plates to move, extend and contract in a transverse direction belonging to the protective body reference plane.

[0054] The protective body has a rectangular shape with four corner regions spaced apart from the intermediate region of the protective body, and at least four corner sliders, preferably at least six corner sliders selected from the group consisting of sliders and additional sliders, are distributed at each end of the two longitudinal support parts and at each end of the two transverse support parts so as to increase the shrinkage of the protective body in the protective body reference plane in each of the four corner regions during filling of the pouch.

[0055] In some options, the protective body portion has a rectangular shape with four corner regions spaced from a middle region of the protective body portion; The sliders include sliders, preferably four sliders, distributed at each end of the two longitudinal support parts, and are adapted to increase the contraction of the protective body part in the reference plane of the protective body part in at least one of the four corner regions.

[0056] In some options, the system further includes a biasing member configured to exert a return action to displace the slider outwardly toward the first position, the first position being a default position in the unfilled and emptied state of the pouch.

[0057] During the filling operation, the filling of the pouch causes a gradual deformation of the protective body portion, generating a pulling action in the protective body portion reference plane to pull the slider inward, the pulling action increasing with the level of filling of the pouch and opposing the biasing action of the return member.

[0058] The biasing member may include one of a leaf spring, a compression spring, and a tension spring.

[0059] In some options, the biasing member is a return member provided with one or more magnetic members, each movable one of which (the so-called drive member) is fixed to or integral with a corresponding / associated slider and configured to be movable together with the associated slider.

[0060] All or part of the slider is provided with a contact part in contact with the abutment surface in the second position, the contact part being a biasing member configured to exert a return action to displace the slider outwardly towards the first position, the first position being the default position in the unfilled and emptied state of the pouch.

[0061] The contact parts may be deformable between an inactive conformation adaptable to the first position of the slider and an active, elastically compressed conformation in which the contact parts are in contact with the abutment surface, the active conformation being assumed inwardly in the protective body part reference plane due to contraction / displacement of the peripheral margin in the filled state of the pouch.

[0062] The contact part may be a porous part, possibly including a foam or alveolar material, which is elastically compressible, and the contact part is in a compressed state in the second position.

[0063] In some options, the contact part presses against the abutment surface in both the first and second positions, and the contact part belongs to a leaf spring or similar spring that is more deformed / compressed in the second position (and therefore excited to form a return member).

[0064] The biasing member may be or form the forward part of the slider that is in contact with the abutment surface.

[0065] The biasing member may be mechanically coupled to the slider such that the slider is biased or pushed outward (back to the default position) by the biasing member toward the first position when the weight of the pouch with the biopharmaceutical composition stored therein is below a threshold value.

[0066] In some embodiments, the protective body is provided with positioning elements that are interface elements between the peripheral margin and the frame structure. Such positioning elements have compressible contact parts that allow sliding, and the contact parts are optionally of different sizes when measured along the radial direction. Such different sizes allow groups of positioning elements in the middle region to be compressed less, allowing for localized restriction of shrinkage of the protective body.

[0067] More generally, some positioning members or similar interface elements may be provided with a deformable part for contacting against an abutment surface of the rigid frame, the deformable part either contacting or being integral with the abutment surface at an intermediate position between the contact end and the peripheral margin of the protective body part.

[0068] The plate can directly or indirectly support a deformable part, such that the deformable part extends around the covering portion of the protective body. An elastic return member or a compressible member can be such a deformable part.

[0069] In some embodiments, the system includes a tensioning element, the tensioning element being displaceable transversely relative to the two longitudinal support parts and coupled to a portion of the peripheral margin. The tensioning element may be configured to pull all or a portion of the peripheral margin outward when the tensioning element is displaced from a retracted position to an extended position. The pulling may be manually operated or performed via a drive member.

[0070] The tension elements may be loosely guided through respective windows or other guide elements provided in a frame comprising the two longitudinal support parts.

[0071] Some embodiments of the present invention also provide a method of assembling a system according to the present invention, the system being a protective system for storing and withstanding freezing and thawing of a biopharmaceutical composition contained within a pouch of a freeze / thaw containment system, the method comprising: - sandwiching the flexible pouch between two plates of a protective body part, optionally with covering portions distributed among the two plates to cover the flexible pouch, the protective body part being configured to protect the flexible pouch and including two plates, the protective body part further having a longitudinal axis and including four sides, the four sides including two longitudinal sides extending parallel to the longitudinal axis and two other side sides; - using a mounting device for fastening two plates together, such that in the assembled state of the two plates the protective body part includes a peripheral margin extending annularly around the covering portion in a protective body part reference plane, the peripheral margin comprising: - at least one opening for receiving at least one port of the flexible pouch; and a plurality of positioning members fixed to or formed on the peripheral margin; Steps and Including, In the assembled state of the two plates, a frame is mounted around the protective body by connecting two longitudinal support parts, distinct from the positioning members, to the peripheral margin, the two longitudinal support parts extending parallel to the longitudinal axis when connected to the peripheral margin and forming two opposite sides of the frame, and a plurality of positioning members connecting the peripheral margin to the frame; The abutment surfaces are contained and distributed between the two longitudinal support parts, and the frame is - with protective body part; - A pouch sandwiched between two plates that restrain the pouch; has become a sustained supporter of a slider forming a positioning member of the plurality of positioning members is slidably mounted on or in the two longitudinal support parts during mounting of the frame, and is movable between a first position and a second position along a direction transverse to the longitudinal axis; - in the first position, in the unfilled state of the pouch, the slider is pushed outwardly by the protective body portion or maintained away from the abutment surface; In the second position, in a filled state of the pouch, the sliders are respectively engaged against one of the abutment surfaces.

[0072] By such a method, an efficient storage unit (forming a cassette) is obtained in a planar configuration before fitting the frame. For high-volume (greater than 50 or 70 liters) flexible pouches, this is of interest since the frame can be made of detachable side members, which can be stored in a reduced space in the disassembled state.

[0073] For example, assembly of the frame may be performed using the following steps: - assembling one side or two parallel sides, preferably short sides (which may each have a C-shaped cross section or any suitable cross section for a sustaining effect), by sliding them onto or around the corresponding marginal areas of the storage unit provided with the positioning members (so that one or two frame sides are positioned below the protective body part at the peripheral margin); and - assembling the two other side parts, preferably long side parts (which can also have a C-shaped cross section or any suitable cross section for a sustained action), by sliding them onto or around the corresponding marginal areas of the storage unit (so that the two frame sides are positioned below the protective body part at the peripheral margins), so as to obtain a frame extending along the protective body part reference plane.

[0074] Such a frame structure allows for rapid assembly and disassembly: a stack of several systems can be obtained, and feet forming vertical spacers between the frames are optionally added and fastened (with a possible additional step to form the system by fastening four feet at the corners of the frame).

[0075] Other characteristics and advantages of the present invention will become apparent to those skilled in the art during the description that follows, given by way of non-limiting example with reference to the accompanying drawings, in which: [Brief explanation of the drawings]

[0076] [Figure 1] 1 is a perspective view of a storage unit according to a first embodiment of the invention before assembling the two plates of the protective body part; FIG. [Figure 2A] 2 is a top view of the assembled storage unit of FIG. 1, in which a ribbed pattern is provided on the upper surface of the protective body portion, including fastening members for directly or indirectly securing a bag thereto. [Figure 2B] FIG. 10 is a side view illustrating an exemplary interlock between two plates, showing a positioning member according to a preferred embodiment, in which the positioning member is connected to a protective body portion at a peripheral margin by an interlocking configuration. [Figure 3]FIG. 1 illustrates a freeze / thaw storage system in which a flexible pouch, in its empty state, is sandwiched between two plates that form a protective body portion, while the peripheral margin of the protective body portion is sandwiched between positioning members. [Figure 4A] FIG. 1 is a perspective view showing a freeze / thaw system using a peripheral frame that houses internal positioning members in a filled configuration, in which the positioning members are inactive to limit inward movement and contraction of the plates that clamp the flexible pouches. [Figure 4B] 10A and 10B are vertical cutaway views illustrating an exemplary integration (inside the frame profile) of a positioning member formed as a slider that is inwardly movable relative to a stationary frame part. [Figure 4C] A detailed view of the freeze / thaw system as shown in Figure 4A, illustrating an optional method for having the lower and upper parts of the positioning member connected to the peripheral margin area (here, the transverse area) without additional fastening pieces. [Figure 4D] 13A-13C show asymmetric pieces that can provide a sustaining function for the protective body portion when coupled to a relief in the peripheral margin. [Figure 4E] A diagram showing an additional positioning member configured to extend around a tubular part of a port provided in a flexible pouch when coupled to a relief in the peripheral margin of the protective body portion. [Figure 4F] FIG. 4B illustrates the front part of the system of FIG. 4A without the front part of the frame to show the positioning member coupled to the peripheral margin front portion. [Figure 4G] FIG. 4B is a top cross-sectional view of a detail of the system of FIG. 4A, but in an unfilled state of the pouch, with some of the internal positioning members adjusted to a modified configuration compared to the other positioning members to selectively limit displacement and contraction of the plate in the intermediate region of the protective body portion. [Figure 5A] A perspective view illustrating an exemplary integration of a positioning member formed as a slider movable inward relative to a stationary frame part in a filled state of a pouch clamped by plates of a protective body part. [Figure 5B] 5B is a perspective view similar to FIG. 5A illustrating a first position of the positioning member formed as a slider, which may be a default position for the unfilled state of the pouch clamped by the protective body portion, and which is obtained either before a filling operation or after a draining operation of the contents of the pouch. [Figure 6A] FIG. 1 is a perspective view of a freeze / thaw storage system capable of supporting and mounting a sample unit, in which some of the internal positioning members are adjusted to selectively limit the displacement and contraction of a plate in the intermediate region of the protective body portion, and the plate is provided with a ribbed pattern. [Figure 6B] FIG. 10 is a vertical cross-sectional view of a detail of the system showing an optional biasing member provided at the interface between the abutment surface of the frame and a sliding positioning member fixed to a peripheral margin part of the protective body portion. [Figure 6C] FIG. 10 is a side view of another optional biasing member provided at the interface between the abutment surface of the frame and a sliding positioning member fixed to a peripheral margin part of the protective body portion. [Figure 6D] 6B illustrates an exemplary distribution of positioning members around the protective body portion when using the same or similar frame as shown in FIG. 6A. [Figure 6E] FIG. 6B is a top view of a portion of the freeze / thaw containment system of FIG. 6A with a sample unit installed in the system. [Figure 7A]A vertical cutaway view showing a positioning member suitable for forming a stopper, configured to slide inwardly into the profile cavity with a limited stroke while retaining a portion of the peripheral margin of the protective body portion. [Figure 7B] 7B is the same vertical cutaway view as FIG. 7A, showing the abutment position, where the positioning members stop inward movement of the corresponding peripheral margin portions of the protective body portion. FIG. [Figure 8] A figure illustrating details of an exemplary distribution of positioning members provided to hold / maintain the same longitudinal sides of the peripheral margins of the protective body portion, making it possible to limit the bulging effect in the middle region of the storage unit in the filled state of the flexible pouch. [Figure 9A] 9 is a top view of the flexible pouch filled with liquid inside the system of FIG. 8, without showing the protective body portion and positioning member. [Figure 9B] 9 is a schematic side view showing a frame-like holder and flexible pouch filled with liquid inside the system of FIG. 6A or FIG. 8, without showing the protective body portion and positioning member. [Figure 10] 5A and 5B respectively illustrate a stacked system as shown in FIG. 4 before and with the pouches filled to show that the pouches remain relatively flat and are still able to expand due to freezing of their contents. [Figure 11A] 10A-10C illustrate steps performed in forming a frame for handling and storing storage units including positioning members, with the optional step of fastening feet to define stackable shelf modules. [Figure 11B] 10A-10C illustrate steps performed in forming a frame for handling and storing storage units including positioning members, with the optional step of fastening feet to define stackable shelf modules. [Figure 11C]10A-10C illustrate steps performed in forming a frame for handling and storing storage units including positioning members, with the optional step of fastening feet to define stackable shelf modules. [Figure 12A] 10A-10C show various states of attachment of the holding and sustaining assembly (here forming a rectangular frame) to hold the storage unit while allowing controlled contraction of the protective body portion. [Figure 12B] 10A-10C show various states of attachment of the holding and sustaining assembly (here forming a rectangular frame) to hold the storage unit while allowing controlled contraction of the protective body portion. DETAILED DESCRIPTION OF THE INVENTION

[0077] In the various drawings, the same reference symbols are used to designate identical or similar elements.

[0078] In the different figures, the vertical, longitudinal, and lateral directions are based on the freeze / thaw storage system being stored horizontally in shelves. The direction perpendicular to the longitudinal direction is the lateral direction. One direction through the height of the freeze / thaw storage system 1 is the vertical direction, which is reflected by direction Z, especially in FIG. 4A.

[0079] In an embodiment of the present invention, the freeze / thaw containment system 1 can be as illustrated in Figures 4A and 6A and includes a protective body portion (12, 112, 212) covering both sides of a flexible pouch 2 for a biopharmaceutical material (hereinafter referred to as biopharmaceutical composition Q).

[0080] 1 to 2A or 3, the protective body portion 12 or 112 includes two plates 12A, 12B for protecting the flexible pouch 2. The two plates 12A and 12B may be fabricated separately. The protective body portion 12 or 112 typically includes ribs on each of the plates 12A, 12B, while the protective body portion shown in FIG. 4A includes at least one outer surface S without ribs.

[0081] The protective body portion 12, 112, 212 is obtained by fastening two plates 12A, 12B together at a peripheral part surrounding the covering portion 8 belonging to the protective body portion 12. For example, the protective body portion 12, 112, 212 can be assembled by fastening the peripheral parts of the plates 12A and 12B together when the covering parts clamp the empty pouch 2. In this regard, a mounting device or mounting system 18 is provided for fastening the two plates 12A, 12B together. In the assembled state of the two plates 12A, 12B, the protective body portion 12, 112, 212 includes a peripheral margin 80. The peripheral margin 80 is obtained by fastening the margin portions 8a, 8b of the plates, respectively. Each plate annular margin can be composed of four outer band regions of the plates 12A and 12B.

[0082] The protective body portion 12, 112, 212 (provided with or without ribs) extends planarly along the protective body portion reference plane P and cannot inflate like a thin rubber balloon because the plates 12A, 12B are relatively rigid to constrain the pouch 2. The protective body portion 12, 112, 212 is typically as rigid as or more rigid than a PET bottle for storing carbonated water, and therefore allows very limited deformation compared to the material of the flexible pouch 2.

[0083] The freeze / thaw containment system 1 is provided with several positioning members PM, which are fixed to or formed on this peripheral margin 80. This peripheral margin 80 can be seen as part of the protective body part, which is complementary to the covering part 8, whereby the pouch conformation changes depending on the level of filling of the pouch 2. The system 1 also includes a frame 15, which is constructed to surround a hollow space through which the pouch 2 extends. The frame 15 can be provided with two longitudinal support parts 31, which are constructed to be distinguishable / separate from the positioning members PM.

[0084] 4B-4G, 5A-5B, 6A-6D, 7A-7B, and 8, the positioning members PM, PM' can be part of the mounting system 18 and / or participate to clamp the two plates 12A, 12B of the protective body part at the peripheral margin 80. The positioning members PM, PM' can be composed of at least two pieces that are distinct and separate from the pouch 2 and the plates 12A, 12B, including several pairs of flat bars UP, LP or UP', LP' that clamp the plates 12A, 12B when using insert projections IP1, IP' or insert pieces IP (e.g., threaded elements) integrally formed with the bars, as the case may be (such threaded elements are provided separately from the protective body part). Typically, the bars UP, LP or UP', LP' are grouped in respective pairs to assemble flat bars above and below the same area of the peripheral margin 80, thus forming positioning members PM, PM'. More generally, the positioning members PM, PM' can be rigid parts, which are typically made from a plastic material (e.g. HDPE) and provided with fastening pieces or integrated fastening means.

[0085] The positioning members PM, PM' are configured to protrude from at least one of the lower surface S' and upper surface S of the protective body portion 12, 112, 212 at the peripheral margin 80, respectively. Typically, the positioning member PM includes a lower part LP and an upper part UP, which are two separate flat bars or any suitable pair of pieces configured to clamp the protective body portion in the area of the peripheral margin 80, outside the hollow space of the frame through which the pouch 2 extends. The lower and upper parts can be identical pieces forming a bar, as in the non-limiting embodiment of FIGS. 4C, 4D, and 4F. Each pair of bars LP, UP forms a positioning member PM, which can be received in or engaged with the frame, as described below. An additional positioning member PM' (different from the other positioning members PM) is illustrated in FIGS. 4E-4F, which allows the port 24 to extend horizontally through the positioning member PM'. More generally, a particular positioning member PM' can clamp a portion of the peripheral margin 80 through which at least one port 24 extends, as shown in Figures 4G and 11A. In some variations, the positioning members can include only members PM that are spaced from the port 24, or can include only members PM excluding any particular members that extend around the port 24.

[0086] 4E-4F, the upper and lower parts LP' and UP' of the positioning member PM' can be attached after the plates 12A, 12B are attached together. The same can be done for the positioning member PM.

[0087] The insert protrusions IP' of each of the parts LP' and UP' are distributed away from the connector parts of the ports 24, here from a central opening OPC that is disposed between the two openings OP1 and OP2 for the passage of the two ports 24. Further ports can extend through the central opening OPC. In the positioning members PM and PM', the insert protrusions IP1, IP' can act as interlocking members or insert parts that cooperate with corresponding reliefs formed in the peripheral margin 80.

[0088] It can be seen that the positioning members PM, PM' typically extend only around the covering portion of the protective body part 12, 112 or 212.

[0089] 6A or 6D, it will be appreciated that the storage unit 10 can be obtained without the protective body part 112 being able to be removed from the frame 15 due to the fastenings provided to hold and maintain the positioning members PM, PM' relative to the respective parts or profiles 91, 92, 93, 94 of the frame 15, wherein the fastenings are adapted to allow the protective body part to move, extend and contract along the protective body part reference plane P, i.e. provide degrees of freedom along at least one of the directions of the axes X and Y shown in FIGS. 1 and 4A.

[0090] When the positioning members PM, PM' are part of a mounting system 18, the mounting system 18 can be considered as an assembly of several displaceable parts that can move inwardly relative to the frame 15. Here, the frame 15 comprises two elongated longitudinal support parts formed by two pieces or profiles 93, 94, each defining a housing for accommodating a respective positioning member PM. At least one of the positioning members PM constitutes a slider that is inwardly movable inside the corresponding housing.

[0091] 3, 4B-4G, 6B-6C, 7A-7B, 8, and 11A, exemplary embodiments can be seen in which the respective lower part LP and upper part UP are two separate pieces configured to clamp the protective body part at a clamping region of the peripheral margin 80. Each clamping region can be elongated parallel to the protective body part edge by extending longitudinally to be at least four times longer (having a length L8) than the maximum width W8 of the positioning member PM, as particularly illustrated in the non-limiting embodiment of FIG.

[0092] 4A, 5A-5B and 7A-7B, all or part of the frame 15 forms a holding and sustaining assembly HR having abutment surfaces AB1, AB2, here provided in two profiles 93, 94, which are exemplary pieces forming longitudinal support parts for supporting the protective body provided with the fastening system 18.

[0093] More generally, the frame 15 typically comprises abutment surfaces AB1, AB2 contained and distributed in two longitudinal support parts, all or part of the positioning member PM connecting the peripheral margin 80 to the frame 15, and the frame 15 being - protective body part 12, 112, 212; - a pouch 2 sandwiched between two plates 12A and 12B; It is understood that the government is committed to sustaining and supporting the

[0094] Some or all of the positioning members PM constitute sliders slidably mounted on or in the two longitudinal support parts and movable along a direction transverse to the longitudinal axis X1 (axis of the protective body part, which may be merged with the longitudinal axis A of the pouch 2) between a first position and a second position: in a first position, in the unfilled state of the pouch 2, the slider is pressed outwards by the protective body part 12, 112, 212 (when it has its flat rectangular shape with maximum perimeter) or is kept away from the abutment surface AB1, AB2, so that the slider can be further displaced inwards; In the second position, in the filled state of the pouch 2, the sliders are engaged against one of the abutment surfaces AB1, AB2 respectively.

[0095] In some options, the positioning member PM can form a guide part for receiving one or more body cross members. Referring to FIG. 5B, a hole 18o can be provided in the positioning member PM for introducing a rod-like cross member that cooperates with a locking part, nut, or bolt. Naturally, slots can be provided in the protective body part 12, 112, or 212 for the body cross member to cross the peripheral margin 80 at multiple locations. However, in a preferred option, as illustrated in particular in FIGS. 2B and 4B-4F, the positioning members PM, PM' can simply clamp the peripheral margin 80 with a discontinuous distribution, while remaining in a state where they cannot be disassembled once they are introduced into the frame 15 (in any elongated cavity CP of the frame 15), typically inside the profiles 91, 92, 93, 94. Thus, there is no need for any additional insert piece IP and the margin portions 8a, 8b may be provided with embossments or boss portions B12, B12' for engagement with corresponding reliefs (cavities CF1) of the positioning members PM, PM.

[0096] 2-3 , the peripheral margin 80 can extend annularly in the protective body reference plane P, and the peripheral margin 80 is provided with at least one opening 80a capable of receiving at least one port 24 of the flexible pouch 2. Two front ports 24 can be provided. The opening or port can be formed, for example, as a closable tube and can be provided between opposing parts of a welded joint where two constituent sheets of the pouch are joined. Such an opening can be of interest to allow the pouch to be filled or emptied. For example, one port forms an inlet for the flexible pouch 2, and the other port forms an outlet for the flexible pouch 2.

[0097] The protective body portion 12, 112, 212 can extend planarly along the protective body portion reference plane P in the unfilled state of the pouch 2. In the illustrated embodiment, the plates 12A, 12B form the covering portion 8, which can be elastically displaced away from the protective body portion reference plane P insofar as the intermediate region MR is concerned by the pushing effect of the walls W1, W2 of the pouch 2 during the step of filling the flexible pouch 2. The covering portion 8 can therefore have a bulged conformation, which is not a stable conformation of the protective body portion 12, 112, 212 when the pouch 2 is in the unfilled state. The plastic material of the protective body portion 12 (which is typically a non-porous plastic material) is configured to elastically return to a stable planar configuration in which the gap between the plates 12A and 12B is planar, i.e., there is no increase in the spacing between the plates 12A and 12B. Here, each plate 12A, 12B is a single molded piece of non-porous plastic material.

[0098] System 1 is suitable for storing and freezing / thawing biopharmaceutical composition Q (see FIG. 7B). Referring to FIGS. 4A and 6A, such system 1 is here horizontally oriented, using a horizontal frame. However, the system could alternatively be vertically oriented, such that pouches 2 can be stored vertically in the cavities of a vertical frame-like holder (see, for example, the pouches described in U.S. Patent No. 5,623,499, which are received vertically by the use of a rigid slotted frame). To form a compact holder capable of accommodating the respective marginal portions of storage unit 10, the use of a rectangular frame 15 (provided with inwardly opening slots or cavities CP) may be of interest.

[0099] The flexible pouch 2 is typically a 2D-type pouch, delimited by two longitudinal sides LS1, LS2 and having a substantially rectangular shape without predetermined folds on its two major outer surfaces, as illustrated in FIG. 1 (empty pouch). Thus, the pouch 2 extends substantially planarly in the unfilled state. The pouch 2 may have two major walls W1, W2. These walls W1, W2 are directly welded to each other at a weld or peripheral seal J and may define an interior volume for storing a biopharmaceutical fluid Q. More generally, the flexible pouch 2 may be of any suitable material for storing a biopharmaceutical composition Q, forming a freezer bag, which may be of a large capacity (typically greater than or equal to 5 L). More generally, the flexible pouch 2 is of a first volume, and the pouch 2 is expandable to have an increased thickness in an intermediate region away from at least four pouch corners, such thickness increasing with the level of filling of the pouch 2.

[0100] Referring to FIG. 1 , the flexible pouch 2 extends in a major plane XY, which here is a horizontal plane. The pouch 2 has a longitudinal axis A parallel to its long sides, which here are two longitudinal sides LS1, LS2 in the non-limiting illustrated embodiment. The flexible pouch 2 is sandwiched between plates 12A, 12B and cannot be removed without removing at least one of the two plates 12A, 12B by separating the plate margins of the same annular shape from the plate margins of the same annular shape (the plates are fixed to each other without any specific fixation between the pouch 2 and either one of the plates). A retention and sustainment assembly HR can be provided in addition to the mounting system 18 to retain the unit consisting of the protective body portion 12 and the mounting system 18. The assembly HR is here provided with a frame 15, which includes slides, frame profiles 93, 94 or similar slotted structures for holding the storage unit 10 at its peripheral margin 80. Figures 4A-4B show an exemplary frame 15 of such an assembly HR.

[0101] Typically, the receiving portion 2r of the storage pouch 2 for receiving the biopharmaceutical composition Q cannot come into contact with the rigid structure of the holding and sustaining assembly HR thanks to the protective body portion 12, 112, or 212. In the assembled state, the protective body portion 12, 112, 212 completely covers the receiving portion 2r of the pouch 2.

[0102] The storage unit 10 provides efficient protection for the biopharmaceutical composition Q stored in the receiving portion 2r of the flexible pouch 2 during freezing, storage, and thawing operations. Due to differences in material, the covering portion 8 of the protective body 12 is less flexible than the receiving portion 2r of the flexible pouch 2 (the covering portion 8 is more rigid relative to the two pieces forming the plates 12A and 12B). When horizontally installed and maintained by the holding and sustaining assembly HR, the two plates 12A and 12B form the lower and upper surfaces, respectively, of the protective body 12, 112, 212. At least one of the lower and upper surfaces is an outer surface of the storage unit, which may optionally be provided with fastening members for directly or indirectly fastening the bag 2′. In the illustrated embodiment, such fastening members 146, 147, 148 for securing the bag 2′ are selectively provided on the frame 15, for example, on corner pieces 15c belonging to the frame 15. The corner part 15c can be in any of the following forms: a piece interposed between two vertical profiles 92, 93, 94 of the frame 15 (as shown in particular in Figures 6A and 6E); - the end parts of such profiles, or - Additional pieces attached onto some of the profiles.

[0103] 6A and 6E, the storage unit 10 can support a bag 2′ thanks to the retaining and sustaining assembly HR, or independently of the retaining and sustaining assembly HR, or in some variations by combining the fastening members of the protective body portion 12 and the assembly HR. This bag 2′ can store a composition representative of a biopharmaceutical composition Q. The volume of the bag 2′ is a second volume that is lower than the first volume, preferably an order of magnitude lower (i.e., at most one-tenth of the first volume). The bag 2′ can be provided with a casing 130, which can be relatively rigid. Such a casing 130 can cover a pouch forming the storage part 200 of the bag 2′.

[0104] The bag 2′ may be provided with fastening elements 132, 133, 134 that cooperate with the fastening members 146, 147, 148 to fasten (directly or indirectly) the bag 2′ to the protective body part 12, 112, 212 and / or the frame 15. The fastening elements 132, 133, 134 may be distributed around the storage part 200 of the bag 2′, which may include a compartment for accommodating the storage part 200, to fasten the casing 130 so that it extends along one of the outer surfaces S, S′ of the storage unit 10. The storage part 200 of the bag 2′ is the part of the bag 2′ that defines the second volume.

[0105] 1 to 4B, the flexible pouch 2 can be directly protected (held in direct contact) by the two plates 12A, 12B of the protective body part 12. To avoid interfering with the conformational changes of the covering portion 8 of the protective body part 12, 112, 212, a positioning member PM is provided at the peripheral margin 80.

[0106] Each pouch 2 can be filled with a solution (fluid composition Q) that is to be frozen and held with slight compression between two plates 12A, 12B that serve as heat exchange surfaces. To this end, the plates 12A, 12B completely cover the pouch 2 at least in the fluid receiving portion 2r, i.e., in the area that defines the internal volume of the pouch 2 (i.e., typically, all walls W1, W2 except for a possible annular seal J and optional outer extensions), as shown in FIG. 1 . In the illustrated embodiment, the pouch 2 is completely covered by a protective body portion 12, 112, 212 formed by the two plates 12A, 12B. During the freeze / thaw operation, the plates 12A, 12B are cooled / heated, for example, by circulating a heat transfer fluid from an external programmable refrigeration unit. The slight compression (storage effect) provides improved contact and heat transfer, resulting in a frozen pouch having the general shape of a pillow (see, inter alia, Figures 4A and 6A).

[0107] The pouch 2 (sandwiched between the plates 12A, 12B) can be placed in a frame 15, preferably a rigid frame that can withstand temperatures below 0°C (preferably not brittle). The frame 15 is of interest to prevent damage to the inner material during handling and transportation. Referring to FIGS. 4A and 6A, the frame 15 can be part of a support structure. Here, the frame 15 is a modular part of a device or shelf (see FIG. 10) that can be positioned in a freezer. In some options, rollers (not shown) can be provided to facilitate transportation. The frame 15 is typically a rectangular protective frame that forms four protective sides of the storage unit 10 while leaving the outer surfaces S, S' of the protective body 12 exposed. The frame 15 can be included in a retention and sustainment assembly HR, which can also include or house a positioning member PM fastened to the peripheral margin 80 of the protective body portion 12, 112, or 212, as shown in Figures 4C-4D, 4F, and 8, among others. The assembly can include a plurality of feet 115, possibly of tubular shape and suitable for stacking. Figures 4A and 11c illustrate non-limiting examples of integration of feet 115 suitable for obtaining a shelf structure such as that shown in Figure 10.

[0108] In some options, spacing between two consecutive frames 15 (at least the spacing between the long sides of the frames) creates inter-unit open space to improve air flow for freezing / thawing the contents of the pouch 2. As illustrated in Figure 10, such vertical gaps also provide accessibility to the protective body portion and its edges for wiping.

[0109] It also provides accessibility to a bag 2' or similar sample unit SU that may be secured onto the outer surface of the protective body portion 12, 112, 212, as illustrated in the non-limiting examples of Figures 6A and 6E.

[0110] More generally, the pouch 2, the protective body part 12, the bag 2′ or similar sample unit SU (if fastened to the protective body part), and the frame 15 can define a freeze / thaw containment system 1 in which the outer surfaces S, S′ (here corresponding to the lower surface S′ of the lower plate 12A and the upper surface S of the upper plate 12B) remain exposed (uncovered), while the flexible pouch 2 is mounted inside the storage unit 10 and is covered by the two plates 12A, 12B. The protective body part 12 has a peripheral margin 80 that is engaged in the gap of the holding and sustaining assembly HR. Storage unit 10 is suitable for use in freezing, storing, and thawing biopharmaceutical fluid / composition Q contained within flexible pouch 2, the fluid typically being introduced after assembling storage unit 10 with flexible pouch 2 (which is typically a disposable pouch) housed within protective body portion 12.

[0111] 4B, 6A and 7B it can be seen that the pouch 2 is inside a protective body part that is sustained by frame profiles 91, 92, 93, 94. The use of four rigid profiles is of interest to form a rectangular frame 15. Optionally, the pouch 2 can be of the Flexboy® type and is therefore a sterile, single-use, disposable container that is adapted to be surrounded by the frame 15 that is obtained after assembling the profiles 91, 92, 93, 94 or similar holding elements.

[0112] In some options, the holding and sustaining assembly HR can have fewer than four members so as not to form a rectangular frame. For example, only three members may be sufficient, with a transverse member interconnecting two longitudinal covering parts 31, 32 parallel to the longitudinal axis A of the pouch 2. FIG. 3 only shows two covering parts 31, 32; the two covering parts 31, 32 can be integral with the feet or associated with transverse structural members. In some options, the covering parts 31, 32 can extend vertically. In the illustrated embodiment, the covering parts 31, 32 extend horizontally, which may be preferred when the pouch stores more than 50 L (e.g., about 75 L, or at least 100 L).

[0113] 3, 4B, 5A-5B, and 7A-7B, pouch 2 can have a configuration or shape that is initially planar in the empty state. Pouch 2 is flexible to allow it to expand and can be made from a pair of flexible sheets (forming respective walls W1, W2) having a rectangular or other planar configuration, joined together at four peripheral edges, providing a containment volume (internal volume for composition Q) between sheets 21, 22, which are spaced apart by a predetermined distance in the filled state. One or more openings or ports 24 can be provided (e.g., formed as closable tubes between opposing parts of the peripheral edges of the sheets) to allow pouch 2 to be filled or emptied.

[0114] Pouch 2 is also designed to provide a high surface area / volume ratio at a low thickness or spacing. By way of non-limiting example, pouch 2 can have rectangular dimensions of about 600 mm by about 1300 mm or 1400 mm, and / or a holding volume of between about 10 liters and about 120 or 200 liters (preferably between 50 liters and 120 liters), and / or a spacing or pouch thickness (height along the Z direction) of between about 8 mm or 10 mm and about 25 mm or 30 mm.

[0115] Each pouch 2 may be made from any suitable biologically compatible material, which preferably promotes heat transfer between the inside and outside of the pouch 2. It is preferred that the material have a lower glass transition temperature than that of the biopharmaceutical material to reduce or avoid damage to the pouch 2 during cryopreservation due to expansion of the biopharmaceutical material. As a non-limiting example, each pouch 2 may be made from a multi-layer composite made solely from a thermoplastic material (e.g., including at least a layer of polyethylene (PE)).

[0116] The protective body portion 12 and the flexible pouch 2 include a longitudinal direction X and a transverse direction Y. The protective body portion 12 and the flexible pouch 2 include respective longitudinal sides and transverse sides. The longitudinal axis X1 of the protective body portion 12 may lie in a central vertical plane separating the two symmetrical halves of each plate 12A, 12B of the protective body portion.

[0117] The pouch 2 optionally comprises one or more tubes T joined (at the transverse sides) to a front end extending transversely to the longitudinal sides LS1, LS2. More generally, the pouch 2 may comprise one hose / tube or any suitable number of tubes connected to the periphery of the useful part of the pouch 2, which here is formed by two main walls W1, W2.

[0118] Protective body 1 and 3-4A, the protective body portion 12 or 112 includes or is composed of two plates 12A, 12B for protecting the flexible pouch 2. The plates 12A, 12B are completely separate here, without any hinged or connecting parts. Typically, the plates 12A, 12B are two separable pieces. These pieces are relatively rigid, for example, sufficiently rigid so as not to form a fold line with a bending angle greater than 45°. Thus, the plates 12A, 12B are configured to remain relatively flat. The protective body portion 12, 112, 212 includes a longitudinal axis X1 and has four sides 120a, 120b, 120c, 120d, including two longitudinal sides 120c, 120d extending parallel to the longitudinal axis X1 and two other sides including a first end side 120a and a second end side 120b that are respectively perpendicular to the longitudinal axis X1.

[0119] 1-3, in each plate 12A, 12B, a first group of ribs is provided with ribs R1, R2, R2', 800 that are located near the peripheral margin 80. An optional second group of ribs may be provided with ribs R3, R4, 83, 84, 85, 86 that are located at a greater distance from the peripheral margin 80. Such ribs of the second group may surround one or two panel portions PP, PP1, PP2, which typically form a rectangular panel, on the respective outer surface S, S' of the protective body portion 12, 112.

[0120] In some variations, the number of ribs may be reduced or ribs may be eliminated.

[0121] In the illustrated embodiment, the protective body portion 12, 112, 212 preferably includes an attachment device / system 18 for fastening the two plates 12A, 12B together, such that in the assembled state of the two plates, the protective body portion 12, 112 includes a peripheral margin 80 extending annularly in the protective body reference plane P, as shown in FIGS. 2A, 3, and 4A-4B. In some options, the peripheral margin 80 extending into the internal gap defined by the frame 15 is typically a margin without ribs. In a variant, one or more ribs R1 adjacent to the margin parts for mutual attachment of the plates 12A, 12B may extend into such a gap. Unlike the weld seal of the flexible pouch 2, which forms a flat annular margin without ribs or reliefs, the peripheral margin 80 may include reliefs forming all or part of the attachment system 18. As can be seen, the relief has a narrow width compared to the elongated ribs R1, R2, R2', R3, R4, 83, 84, 85 provided in the covering portion 8 of the protective body part 12,112.

[0122] The protective body portion may be provided with a first end side 120a and a second end side 120b: the first end side 120a is constituted by the ends E1 of the two plates 12A, 12B in the assembled state of the protective body part 12, 112, 212; the second end side 120b is constituted by the ends E2 of the two plates in the assembled state of the protective body part 12, 112; One or more ports 24 may project axially outward from second end side 120b, so that a portion of the pouch front edge is now accessible.

[0123] In the empty state of the pouch 2, the two plates 12A, 12B respectively form a first surface S' and a second surface S of the protective body portion 12, 112 that covers the pouch 2. When having a substantially horizontal configuration, the first surface is the lower surface and the second surface is the upper surface. In some options (not shown), all or part of the fastening members 146, 147, 148 may be provided on one of these surfaces S, S' near an end side selected from the first end side 120a and the second end side 120b.

[0124] At least one of the lower surface S′ and the upper surface S can be a surface having a plurality of ribs distributed over two longitudinally opposite parts of the surface, preferably including a first transverse rib portion 4 proximate the first end side 120 a and a second transverse rib portion 6 proximate the second end side 120 b.

[0125] Such transverse ribs provide an accordion effect due to the width of the corresponding grooves G1, G2 formed by the ribs and / or the height of the ribs (depth of the grooves G1, G2). This promotes localized expansion of the plates 12A, 12B despite the planar structure of the peripheral margin 80 that forms the protective reference plane P. Typically, in the corner regions CR, the first and second transverse rib portions 4, 6 have heights that decrease as the spacing from the corner apex of the plate containing such rib portions 4, 6 decreases. Thus, excessive expansion, which could result in undesirable folding (along diagonals), can be limited or prevented by reducing the height of the corner rib portions extending into the corner regions CR. In other words, the accordion effect can be effectively reduced in the four corner regions CR of each plate 12A, 12B. More generally, it is useful to structure plates 12A, 12B with first and second transverse rib portions 4, 6 to promote spreading of fluid toward margin 80 and toward the corners of protective body portion 12, 112 when filling a flexible pouch 2 sandwiched between plates 12A, 12B.

[0126] This is of interest in order to have or improve abdominal retention effects. Indeed, the more fluid can be distributed toward the four corners, the less the pouch 2 will bulge in the middle region. The protective body portion 12, 112 can typically move within the gaps of the retention and retention assembly HR, as explained in more detail below. Moreover, the structuring effect of the ribs can prevent fold lines from forming substantially along the diagonals DL1, DL2 when the difference in thickness / expansion between the middle region, including the center C of the protective body portion, and the covering portion edges is too significant.

[0127] Some detailed embodiments of the protective body part 12 or 112 provided with a ribbed pattern will be described hereinafter.

[0128] Plates 12A, 12B, as shown in FIGS. 1, 2A-2B, 4A-4C, 4F-4G, and 8, correspond to a first embodiment of the protective body 12, in which several ribs are provided. On the outer surface of each plate, ribs are provided so that the inner surface is provided with grooves. Some grooves G1, G2, such as those shown in FIG. 1, include transverse groove portions that extend perpendicular to the longitudinal axis X1 and near the opposite end sides 120a, 120b of the protective body. An annular rib R1 (protruding upward from the outer surface S or S') may be provided to define the groove G1, which is annular in shape on the inner surface of the plate. Two separate ribs R2, R2' projecting upwards on the outer surface S or S' may be provided so as to define one or two grooves G2, each of which is of annular or partly annular shape on the plate inner surface.

[0129] Thanks to the ribs R1 and R2, R2', a pair of transverse rib portions 4, 6 (here parallel to the Y axis (perpendicular to the longitudinal axis X1)) can be positioned near each end side 120a, 120b. In other words, these ribs form a first transverse rib portion 4 proximal to the first end side 120a and a second transverse rib portion 6 proximal to the second end side 120b.

[0130] 1-2A, it can be seen that each plate 12A, 12B can be rectangular with four corner regions CR, two imaginary diagonals DL1, DL2 (plate diagonals) that intersect a pair of corner vertices of the four plate corners, respectively. More precisely, each of the two imaginary diagonals DL1, DL2 intersects: a first series of corner ribs C1, C2 located proximal to the first end side 120a and projecting outward along a direction perpendicular to the protective body reference plane P; a second series of corner ribs C1', C2' located proximal to the second end side 120b and projecting outward along a direction perpendicular to the protective body reference plane P; Each of the corner ribs C1, C2, C1', C2' is curved and connects two rib portions that are perpendicular to each other, so here, the annular rib R1 can include two pairs of corner ribs C1, C1', respectively.

[0131] While the embodiments of Figures 1, 2A-2B and 4A show a ribbed pattern (where the ribs can be thought of as peripheral ribs arranged around the central panel portion PP of plates 12A, 12B), Figures 3 and 6A show that ribs can be provided in the intermediate region MR, possibly extending transversely to separate two panels PP1, PP2 of the same plate.

[0132] Although the same ribbed pattern is provided in the two complementary plates 12A, 12B in the embodiments of Figures 1-3 and 4A-4B, 6A, in variants some differences may be provided. Optionally, one or two of the plates may be devoid of ribs.

[0133] Plates 12A, 12B form reinforcing layers when overlapping (and preferably completely covering) major walls W1, W2, respectively. The thickness of each plate 12A, 12B before thermoforming is approximately 1.27 mm and / or may be less than 2 mm, and the plastic material of the plates has a modulus of 1.10 g / cm 3 Density greater than 1.15 g / cm 3 Density above 1.5 g / cm 3 or 1.6 g / cm 3The plate material may have a tensile strength at break that is typically between 45 MPa and 75 MPa, for example in the range of 50-60 MPa, typically in the range of 52-59 MPa (standard test ASTM D638). The plate material may have a tensile strength at break between 45 MPa and 60 MPa, and may have a Young's modulus along both the transverse direction (TD) and the machine direction (MD) comprised between 1250 MPa and 1550 MPa.

[0134] Although the illustrated embodiment shows the protective body portion 12 completely covering the two main walls W1, W2 with the covering portion 8, other sizes may be used for the covering portion 8. For example, the protective body portion 12 may cover only a transverse band portion of each wall W1, W2 at a predetermined distance from one of the two opposite pouch edges. Moreover, one or more complementary protective body portions may be used to cover at least one of the end parts of the walls W1, W2.

[0135] Embodiment details regarding the mounting system for attaching the plates together The protective body part 12 can have a covering portion 8 for covering the pouch 2 and two opposite margin portions 8a, 8b on two longitudinal sides 120c, 120d of the protective body part 12. In the unfilled state of the pouch 2, the protective body part 12 extends flat along a protective body part plane P and remains flat. The plates 12A, 12B remain attached at several locations on the peripheral margin 80 during handling of the system 1 thanks to the attachment system 18.

[0136] The protective body portion 12 can be transparent, for example, as is the pouch 2. The plates 12A, 12B can have a general curvature but cannot bend easily (their flexibility is substantially as low as that of PET). The peripheral margin 80 can form an annular attachment area where bending is not permitted.

[0137] 2, the protective body part 12 is also provided with a mounting system 18 for fixing the two plates 12A, 12B to one another around the covering part 8. The plates 12A, 12B can be removably fixed to one another by the mounting system 18, which is distributed in a peripheral margin 80.

[0138] Optionally, the attachment system 18 can include multiple snap buttons. The plates 12A, 12B are provided with several interlocking means, which are arranged, for example, in pairs, with one of the two plates 12A, 12B including a first element of a snap button and the other including a second, complementary element of a snap button. Referring to FIG. 2A, the second element 18b (possibly a male element) engages with the first element 18a (possibly a female element) in a direction parallel to the vertical axis Z. More generally, it will be understood that any interlocking means formed as reliefs in the peripheral margin 80 can be distributed among the plates 12A, 12B. Each of the reliefs of a given plate 12A projecting toward the other plate 12B can be fitted (possibly loosely fitted) into a corresponding hollow relief projecting away from the plate 12A, and vice versa.

[0139] Alternatively, the mounting system 18 is a non-removable system, which means that once the two plates 12A, 12B are fixed to each other, it is no longer possible to remove the two plates 12A, 12B from each other.

[0140] It may be advantageous for protective body portions covering large sized pouches to have the relief in the attachment system 18 contained only within the peripheral margin 80, thus minimizing pieces and facilitating the fastening action. Moreover, the relief formed by such an integral attachment system 18 can serve as a discrete anchoring part for easily installing and securing the positioning member PM, as will be further explained with reference to FIGS. 2B and 4B-4G.

[0141] In the non-limiting embodiment of FIGS. 1 to 2A, the protective main body portion 12 includes: - snap buttons 18a, 18b on the transverse sides 120a, 120b and on the two marginal portions 8a, 8b; and / or - apertures 102 for receiving insert pieces IP or similar anchoring elements not included in the plates 12A, 12B (see Figures 5A-5B and 7A); It is possible to include:

[0142] In the option of using snap buttons or similar fastening parts included in the plates 12A, 12B, such fastening parts may be symmetrically arranged on the transverse edges of the two plates 12A, 12B. Alternatively, the protective body part 12 may include more snap buttons on the front side 120a than on the rear side 120b.

[0143] More generally, the attachment system 18 may typically include any suitable mechanical fasteners disposed between the covering portion 8 and the longitudinal sides 121, 122. Typically, the two opposing margin portions 8a, 8b may be considered as part of a fastening assembly provided to prevent any shifting movement of the position between the two plates 12A, 12B once the two plates 12A, 12B are fastened to one another at the at least two margin portions 8a, 8b.

[0144] 1, 2A-2B, and 4B-4C, the mounting system 18 includes first and second elements 18a, 18b, which may be identical or similarly fabricated and distributed between the lower plate 12A and the upper plate 12B, respectively. With such a configuration, the plates 12A, 12B may be identical. Here, the first element 18a belongs to the first plate 12A, while the second element 18b belongs to the second plate 12B. The interlocking means may be formed by alternating outwardly projecting boss portions B12 and inwardly projecting boss portions B12' at the peripheral margin 80.

[0145] Such boss portions B12, B12' may be hollow so that they can simultaneously act as male and female members. For at least some of these boss portions, each boss portion: - male members for guiding and fixing the parts LP, UP of the positioning members PM, PM', and - Female member for interlocking function in mounting system 18 It is possible to simultaneously participate as and / or, with respect to at least a portion of the boss portions, each boss portion is: - a male member that fits / is received in a hollow portion of a corresponding boss portion (of the other plate); and - Female member for guiding and fixing the parts LP and UP of the positioning members PM and PM' It is possible for each of them to participate as

[0146] It can be seen that the boss portions B12' are thinner than the boss portions B12. They can be removably fitted inside the boss portions B12'. In a given plate 12A or 12B, the boss portions B12' are oriented inward so as to protrude from the opposite outer surface of the plate. The boss portions B12' can be snap-fit inside the hollow portions of the boss portions B12, allowing them to protrude beyond the reference plane without protruding beyond the other plate (eliminating the need for through-holes in the plates 12A, 12B). More generally, the first and second elements 18a, 18b can be configured such that the protective body portion 12 is a two-piece body that can extend along its reference plane P without any additional fastening means and without accidental removal to protect the pouch 2. The positioning members PM, PM' can be thought of as intermediate pieces for interconnecting the protective body portion 12 to the frame 15.

[0147] The insertion of the positioning members PM, PM' in the peripheral margins 80 is sufficient to allow the parts LP, LP', UP, UP' to be fixed to the corresponding plate 12A or 12B by a clamping effect due to the boss portion B12, typically using outer clamping reliefs RS formed in the side walls of the boss portion B12, as illustrated in the non-limiting example of Figure 2B. In other words, before fastening the plates 12A, 12B together, the lower parts LP, LP' can optionally be fixed to the lower plate 12A and the upper parts UP, UP' can optionally be fixed to the upper plate 12B.

[0148] Here, the boss part B12' can then be inserted into the hollow of the boss part B12 to form the protective body part reference plane P. The inner wall bounding the hollow of the boss part can be slightly tapered towards the access opening so as to provide a holding effect without preventing full insertion of the boss part B12'. The outer clamping relief RS can be engaged axially and radially over the tapered part of the inner wall.

[0149] Although the figures show attachment of the pieces forming the positioning members PM, PM' by a substantially linear bayonet action using two bayonet areas, other couplings may also be involved, possibly by first engaging a pivot socket or pivot insert of such piece around a coupling relief formed in the peripheral margin 80, followed by rotation of such piece, for example about an axis parallel to the Z direction. The final position of the pivoting positioning member may be locked using clips and / or abutment parts.

[0150] Here, the boss portions B12, B12' are provided to allow the plates 12A, 12B to be removably fixed to one another, and the boss portion B12' acts as a male member in the interlock of the mounting system 18 to cooperate with a corresponding hollow portion of the boss portion B12. Typically, the first boss portion B12 defines the boundary of the hollow portion and the second boss portion B12' is received by plastic retaining contact. Here, the second boss portion B12' is a protrusion (preferably a hollow protrusion) that projects inward from the corresponding plate 12A or 12B perpendicular to the plane P.

[0151] More generally, plates 12A, 12B may be removably secured to one another by any suitable attachment system 18. Such a system 18 may also be of the type specifically seen (schematically illustrated) in FIGS. 3, 5A-5B, and 6C. In some options, plates 12A, 12B support interface pieces that overlap the attachment area defined by attachment system 18 without interfering with the attachment between the two plates 12A, 12B. Such interface pieces (possibly including elastically deformable parts or discontinuous surfaces for contact with abutment surfaces) are removably mounted on peripheral margin 80. In other options, all or some of these interface pieces, which interface with peripheral margin 80 and the covering parts of retention and sustainment assembly HR, act as fasteners to maintain plates 12A, 12B in a planar state around covering portion 8.

[0152] 2A-4G, 6A-6B, and 7A-7B, when the two plates 12A, 12B are fixed to each other, they sandwich the flexible pouch 2. The planar plate 12A (which forms the lower surface S' of the protective body portion 12) presses the lower surface of the flexible pouch 2 against the vertical axis Z. Similarly, the planar plate 12B (which forms the upper surface S of the protective body portion 12) presses the upper surface of the flexible pouch 2 against the vertical axis Z. The two plates 12A, 12B can have planar dimensions that are substantially the same as those of the flexible pouch 2.

[0153] Retention and Sustainment Assembly 3, 4A-4B, 4F, and 6A-6E, the retaining and sustaining assembly HR includes a frame 15 and positioning members PM, PM', which either cooperate with or are part of the mounting system 18. The positioning members PM, PM' (here covering the mounting system 18 by clamping a portion of the peripheral margin 80) can move relative to the frame 15, which acts as a stationary part of the retaining and sustaining assembly HR. In some embodiments, the two longitudinal covering parts 31, 32 comprise profiles and can also be considered as belonging to the retaining and sustaining assembly HR. The positioning members PM, PM' can be introduced into the profile of the frame 15 or can be attached to similar covering parts 31, 32 before assembling the assembly HR (typically before assembling the frame 15).

[0154] 5A-5B, 7A-7B and 8, the positioning members PM can comprise insert parts or can be associated with insert pieces IP, which belong to a mounting system 18 for keeping the protective body part 12 assembled. In such an option, the plates 12A, 12B are provided with through-holes. In some variations, the plates 12A, 12B can comprise overmolded parts integral with the peripheral margin 80, which form positioning members having a lasting effect when received in or engaged in any suitable manner with the covering parts 31, 32 of the assembly HR.

[0155] More generally, two covering parts (such as those shown in FIG. 3 ) are arranged to maintain two longitudinal margin portions 8a, 8b of the peripheral margin 80 while allowing the two plates 12A, 12B to move, expand, and contract in a transverse direction relative to the protective body reference plane P. As shown in FIGS. 4A and 6D-6E , the two longitudinal covering parts 31, 32 can include two profiles 93, 94 that respectively define internal cavities CP. In a non-limiting embodiment, the gap can be the internal cavity CP of each of such covering parts. Each of the two longitudinal covering parts 31, 32 can include a substantially C- or U-shaped profile to define one of the internal cavities CP.

[0156] 2A-2B and 6A, it can be seen that the pouch 2 is sandwiched between the plates 12A and 12B without interfering with the hose or tube T provided with the end connector 17, respectively. The protective body portion 12, 112, 212 can be assembled first, and then the two protective parts 31, 32 are assembled to complete or cover the mounting device 18.

[0157] Typically, the holding and sustaining assembly HR comprises a frame 15 provided with four sides (here rectangular in shape). The longitudinal covering parts 31, 32 may be protected in profiles 93, 94 forming the two longitudinal sides of the frame 15. Other covering parts provided along the transverse sides of the protective body part 12, 112, 212 may also be included in the mounting system 18. Optionally, such other covering parts may be housed / protected in the profiles 91, 92 forming the two transverse sides of the frame 15.

[0158] More generally, several profiles can form all or part of the frame sides. Preferably, at least four rigid profiles 91, 92, 93, 94 arranged in a rectangular fashion form the four sides. Two of the four profiles are included in or form two longitudinal covering parts 31, 32. These two profiles 93, 94 are formed as two longitudinal slides for respectively receiving at least three of the positioning members PM separated and distributed along the length of the frame 15. Optionally, the two other profiles 91, 92 can also form slides (here, transverse slides) for accommodating the transverse sides 120a, 120b of the protective body part 12, 112, 212. Similar positioning members PM, PM' can be slidably mounted in the rail-like profiles 91, 92.

[0159] The holding and sustaining assembly HR can maintain the protective body portion horizontally or vertically, and the frame 15 is also useful for forming peripheral protection around the protective body portion 12, 112, 212. The peripheral frame 15 accommodates internal positioning members PM, PM' having a predetermined size along the Z direction, which is larger than the corresponding size (along the same direction) of the openings in the open sides of the profiles 91, 92, 93, 94. Four similarly constructed profiles 91, 92, 93, 94 are provided here to accommodate a positioning member PM on each of the four sides, but variations having one or two sides without such positioning members PM can also be provided. Furthermore, variations with different types of covering parts 31, 32 can be provided either with the ability to have shrinkage management on some sides of the protective body portion 12, 112, 212 or without the possibility of having such shrinkage management (for example, if the volume of the pouch 2 is relatively low).

[0160] The structure shown in FIG. 4A is of interest for relatively large volume pouches 2, which can have significant bulge B without shrinkage control at the peripheral margins 80.

[0161] 4A-4G, 5A-5B, 6A-6D, and 7A-7B, an exemplary embodiment for forming the positioning members PM as stoppers that prevent excessive inward displacement of some areas of the peripheral margin 80 as the pouch 2 becomes increasingly filled will be described. Here, the frame 15 is provided with abutment surfaces AB1, AB2 or rim portions BS1, BS2 contained in the abutment members. Each abutment member can define an inner access to the housing, and the positioning members PM, PM' extend into the housing. Here, each profile 91, 92, 93, 94 forming the side of the frame 15 can be provided with an open end suitable for introducing a respective side (selected from among the four sides) of the protective body portion 12, 112, 212 into the inside of the housing. Such open ends can be closed by corner sections 15c fastened to profile end supports. The inner open side (formed by the inner open section 15a of the frame 15) is not used for the assembly or disassembly steps due to the presence of the abutment members BS1, BS2, which prevent the positioning member PM from being inserted inside the profile or extracted outside the profile through the inner open side. Indeed, on the inner face of each profile 91, 92, 93, 94 there is present at least one abutment member BS1, BS2 extending transversely to the protective body part reference plane P.

[0162] In the illustrated embodiment, the positioning members PM mounted within the long margin portions 8a, 8b of the peripheral margin 80 have a constant size at least along the X and Z directions. In some variations, the inner open side can have at least one through-opening that allows insertion of the positioning members PM having a first compact configuration, in which they are fixed to the peripheral margin 80. After such insertion, the positioning members are expanded to have a second configuration that prevents extraction of the positioning members through the inner open side. In such a second configuration, the positioning members remain fixed to the peripheral margin 80 by fastening parts (which are typically stationary parts). To achieve such an expansion effect, a telescopic configuration of the positioning members (with telescopic expansion available along the X or Z axis), an expandable material, or a hinged structure can be used. In their second configuration, the positioning members PM can be supported by abutment members BS1, BS2. The frame 15 may have another open section to access and (preferably reversibly) actuate the dilation effect.

[0163] The positioning members PM, PM' may be adapted to cover boss portions B12, B12' (such as those illustrated in Figures 2A-2B and 4C) or similar embossments. For example, the positioning members may include several cavities each accommodating a respective pair of boss portions B12, B12', as in the example shown in Figures 4C-4G, among others. With such an arrangement, there is no need for apertures or through-holes in the margin portions 8a, 8b of the plate (only one hole may be provided for at least one port 24 at the front end of the protective body portion).

[0164] Typically, the frame 15 can accommodate the margin portions 8a, 8b sandwiched between multiple discontinuous positioning members PM. Along the Z direction (see FIGS. 1 and 4A-4B), the depth of each hollow defined by the boss portion B12 or B12′ (such depth defining the stroke for disengagement between the complementary boss portions B12 and B12′) can exceed the maximum distance (measured along the Z direction) between the frame 15 and any one of the positioning members PM. In such an option, the frame 15 thus extends above and below each of the positioning members PM, PM′, preventing accidental disassembly of each pair of boss portions B12, B12′ (which are part of the mounting system 18). Such a configuration can facilitate easy attachment and detachment of the positioning members PM, PM′, allowing quick attachment after obtaining the assembled configuration of the protective body portion 12, 112, 212.

[0165] 4A-4D, 4F, and 12A-12B illustrate a frame 15 having profiles 91, 92, 93, and 94, each of which is provided with one or more elongated cavities. Each cavity CP is vertically bounded between a lower section HP1 (preferably formed by horizontal walls) and a lower section HP2 (preferably formed by horizontal walls). Furthermore, the cavity CP is bounded between an inner open section 15a and an outer section 15b, which may form the outer surface of the frame 15.

[0166] Outer section 15b may form part of a side wall (which here is a rectangular side wall) of frame 15. Four elongated profiles 91, 92, 93, 94, and optional corner section 15c for interconnecting adjacent two of the elongated profiles, may form the outer side wall of frame 15 and thus define an outer perimeter (here a continuous perimeter) of frame 15.

[0167] Here, each profile 91, 92, 93, 94 has or includes a C-shaped section, with the inner open-sided opening in section 15a being bounded between two vertically spaced abutment members BS1, BS2. Each abutment member is here a continuous member elongated along the length of the corresponding profile. However, in variants, the abutment members BS1, BS2 may be divided into separate abutment regions or constructed in any suitable manner without interfering with the protective body reference plane P. In the embodiment of FIGS. 4A and 12A-12B, the profiles have additional cavities above and / or below the elongated cavity CP, allowing the height of the profiles 91, 92, 93, 94 to be much greater than the height of the cavity CP (e.g., at least twice as great). The positioning members PM, PM' may be compact in height to be accommodated in such cavities CP, such that they are no taller than their radial extension (transverse extension perpendicular to the axis X1, for the longer profiles 93, 94). The length of each positioning member PM, PM' may be longer (preferably at least three times longer) than any other size of the positioning members PM, PM'.

[0168] 11A and 11B or 12A, the positioning member PM can be removably fastened to the peripheral margin 80 around the covering portion 8. The positioning member PM arranged on the rear side (here, opposite to above at least the port 24) and the positioning member PM arranged on the two margin portions 8a, 8b are then inserted into the corresponding cavities CP of the profiles 91, 93, 94.

[0169] After attaching the positioning members PM; PM', the first profile 91 can be positioned to accommodate the rear marginal portions of the protective body part 12 by a predetermined sliding displacement. The positioning members PM in the two marginal portions 8a, 8b are then also received in the elongated cavity CP by sliding insertion along a direction parallel to the long sides of the profiles 93, 94 in which they are accommodated. The respective parts LP and UP, or any appropriate piece of the positioning member PM, can therefore be inserted behind the abutment members BS1, BS2 and remain behind the abutment members BS1, BS2 in the assembled configuration of the frame 15 around the protective body part 12, 112, 212. In other words, each of the abutment members BS1, BS2 can be configured to separate a hollow space (for the pouch 2) from the cavity CP in which the respective positioning member PM can be accommodated.

[0170] Corner sections 15c may be used as shown in the embodiment of Figures 12A-12B. At least two corner sections 15c may be fastened to the transverse profile 91 (which here is the rear profile) before or after installing the longer profiles 93, 94. Positioning members PM, PM' may be arranged on the outside of the corner sections 15c.

[0171] With regard to the positioning members PM, PM' received in the final profile 92 (the last one to be assembled, here the front profile 92), Figures 4F, 6A, and 12B show that the particular positioning member PM' is modified in its intermediate part, deprived of the insert portion IP1 or cavity CF1 for receiving the boss portion B12. Indeed, along such intermediate part, the protective body part 12 has an opening 80a in a narrow region adjacent to the positioning member PM', and the port 24 of the pouch 2 extends longitudinally away from the covering portion 8 of the protective body part 12, across such opening 80a and across such intermediate part, through the through openings OP1, OP2 shown in Figure 4E.

[0172] Moreover, all or part of the profile can be obtained by assembling at least two contoured pieces. For example, FIG. 12B shows two pieces 92a, 92b superimposed to define a cavity CP for receiving the positioning member PM and the positioning member PM′ (which here is a central positioning member intersected by the longitudinal axis X1 of the protective body part 12). The two pieces 92a, 92b are assembled to form the profile 92 of the frame 15 (the profile 92 as shown in FIG. 4A). The inner section 15a of the profile 91 composed of the pieces 92a, 92b can include the innermost wall of the piece 92a and the innermost wall of the piece 92b. The outer section 15b can be formed of a simple wall or a double wall, optionally provided with a window 9d for the passage of a clamping member C9. Each clamping member C9 can be used to hold a tubular portion of a hose T connected to one of the ports 24. 11A-11C and 6A-6D, each longitudinal support part (typically underlying in the form of a profile 93, 94 or similar piece) defines one or more housings and is assembled with at least one adjacent support part (e.g., two transverse support parts) (also possibly underlying in the form of profiles 91, 92). In some cases, an annular housing may be included in the frame 15 when the profiles 91, 92, 93, 94 are assembled, using a lower foot 115 and / or an upper foot 116 for supporting another frame 15 (see also FIG. 10). For example, the two profiles 93, 94 define a first housing and a second housing, respectively, in which the slider is mounted.

[0173] Here, the slider - a first slider fitted into at least one cavity CP defined by the first housing; - a second slider fitted into at least one cavity CP defined by the second housing; and It can be seen that it is possible to include

[0174] 8 and 11A, it can be seen that the sliders in the first and second housings will act as stops, more particularly either as early stops 41 when mounted in an inwardly shifted manner on the peripheral margin 80, or as later stops 41′, 42 which engage abutment members BS1, BS2 at a later stage during filling of the pouch 2. The front surface BS of the early stops may, as the case may be, already be engaged on one or more of the abutment members or rim portions BS1, BS2 provided on the frame 15 (here, in the intermediate region MR as an option in FIG. 3) for the unfilled state of the pouch 2.

[0175] 11A, each transverse support part (here formed as profile 91 or 92) is configured to receive an additional slider, at least part of which acts as an early stop, the front surface BS′ (oriented towards pouch 2) of which may possibly already be engaged on one or more of the abutment surfaces provided in frame 15 (here in transverse profiles 91, 92 or similar transverse support parts of frame 15) for the unfilled state of pouch 2.

[0176] In the embodiment shown, all or some of the positioning members PM are configured to slide, thus forming sliders that can be displaced inwards as the filling level of the pouches 2 increases. A first group of these positioning members PM is distributed longitudinally on the long sides of the frame, while a second group of positioning members PM is located along the transverse area of the peripheral margin 80 and is distributed on the short sides of the frame. The sliders, housed in profiles 91, 92 or mounted on similar transverse support parts, are each slidably mounted so as to be movable along the direction of the longitudinal axis X1.

[0177] The frame 15 here has a rectangular shape thanks to the two longitudinal support parts and the transverse support parts, and it is therefore understood that the frame 15 comprises abutment surfaces, which are distributed among the two longitudinal support parts and among at least one of the transverse support parts.

[0178] Tubing Holder 6A, one or two hoses or tubes T are typically connected to the front edge of the flexible pouch 2. The rear edge of the flexible pouch 2 can extend substantially parallel to the front longitudinal edge at its opposite longitudinal end. Each tube T can be bent and have a length that exceeds the length of the longitudinal sides LS1, LS2 of the pouch 2, although any size hose / tube can be used. Each tube T can be maintained substantially parallel to the protective body reference plane P by attachment to a tubing holder provided in or attached to the frame 15 of the assembly HR.

[0179] Each hose / tube T is provided with a connector 17 for fluid connection (typically to another biopharmaceutical device). The connectors 17 thus allow the flexible pouch 2 to be fluidly connected to another element (e.g., a tank). In the storage position of the tubes by use of the fixing means MF1, MF2, each connector 17 can be positioned between the longitudinal rear side 120b and the middle region MR of the protective body part 12.

[0180] 4A, one or more of the elongated profiles (here, profile 94) may be provided with one or more fixing means MF1, MF2 for supporting at least one tube T connected to port 24 or contained within pouch 2 as an extension defining port 24. The tubing holders (including fixing means MF1, MF2) may be distributed in at least two spaced locations along the sides of frame 15 in the peripheral area of system 1.

[0181] In the exemplary embodiment, each corner section 15c has a transverse extension 15d formed as an internal part, adapted to be inserted inside the profile 92, which is provided with an opening 92o for the port 24. Such extension 15d extends linearly from the corner section external part toward the opening 92o and includes a clamping member C9 formed as a respective bracket for holding a hose / tube T. Each clamping member C9 can be disposed between the port 24 and the external part of the front corner section 15c. Each clamping member C9 protrudes outward from the outer section 15b of the profile 92 through a corresponding window 9d formed in the outer section 15b. Referring to FIGS. 4F, 4G, and 12B, the profile 92 here includes two parts 92a, 92b, which have an overlapping region for their outer walls that form the outer section 15b. An extension 15d may extend along such outer section 15b and delimit the rear part of the elongated cavity CP of the forward profile 92.

[0182] Each bracket of the clamp member C9 has two flexible branches that define a suitable spacing for hose insertion so that the clamp member C9 can be used to hold a tubular portion of a hose T connected to one of the ports 24.

[0183] More generally, the frame 15 can be provided with clamping members C9 and / or grooves G9 for holding one or two hoses / tubes T connected to the pouch 2 via the ports 24, thus forming a tubing holder. Such a tubing holder has holding parts distributed over at least two or three profiles 92, 93, 94 and optionally one or two corner sections 15c. Here, one or two profiles arranged perpendicular to the front profile 92 preferably include part of such holding means for holding the hose T above the protective body part 12. Depending on the ease of access to the top or bottom of the protective body part, the tubing holder can also extend below the protective body part 12 in some variants using grooves G9 arranged below the protective reference plane P.

[0184] It will be appreciated that the tubing holder is located completely outside the cavity CP so as not to interfere with the peripheral margin 80 and therefore with the freedom of movement of some of the positioning members PM, PM'. When groove G9 is provided in the longer profiles 92, 94, groove G9 can be substantially as long as the flexible pouch 2 and / or can be substantially as long as the space delimited between the opposing transverse profiles 91, 92. This allows flexibility in using groove G9 to position the fixing means MF1 provided with anchor fixing pieces.

[0185] In a first option, the fixing means MF1 of the tubing holder include one or more anchoring pieces with anchoring reliefs 160 having a shape complementary to the receiving grooves G9 of one of the longer profiles 93, 94. Each anchoring piece may also be provided with an abutment end 162 in contact with a surface (here, a substantially vertical surface) of the inner section 15a. The anchoring pieces may extend upward from a joint part joining the anchoring reliefs 160 and the abutment end 162; such joint part may optionally be a hollow or recessed part, improving the deformation of the anchoring reliefs that may be clipped into the grooves G9. At their upper ends, the anchoring pieces further include a fastening member 147 for holding the sample unit SU parallel to the frame 15 (and thus, in the illustrated embodiment, substantially parallel to the reference plane P). Such a single-piece construction of the fixing means MF1 simplifies the mounting step. It may also be of interest to accommodate two or more components, especially when it also has a sample unit SU supported by fixing means MF1 (the positioning of which is easily adjustable in length along profile 93 or 94).

[0186] It can be seen that the sample unit SU is mounted above the two longer profiles 93, 94 at a predetermined distance from the rear corner section 15c, and also by one or more fastening members 146 located at the rear end of the frame 15. In some options, such additional fastening members can be formed near the rear end of the protective body part (typically outside the peripheral margin 80).

[0187] Referring to the options illustrated in Figures 4C and 6E, the hose / tube T is in the groove G9 (in the part of the groove G9 that is remote from the rear profile 91 and close to the front profile 92), and - In the blocking groove BG of the anchor fixing piece It can be simultaneously accepted and / or guided. This is of interest in order to have a compact arrangement of the entire system 1, the outer periphery of which is bounded only by a profile (here by the outer section 15b of the frame 15), which effectively acts as protection for the pouch 2 already clamped between the two plates 12A, 12B.

[0188] The fixing means MF1 is easily removable, as a simple rotation of the anchor fixing piece may be sufficient to release this piece from the groove G9. There is no need for a tool to remove the hose / tube T from the guide groove G9, because the tube end is already available / outside of such groove G9 by being clipped into the blocking groove BG, which is very short compared to the elongated groove G9.

[0189] 10 and 11C, the fixing means MF1, MF2 can comprise at least one fixing element 110, which here can be snapped onto the frame 15 by engaging onto an outer part of a rail-like profile of the frame 15. For example, the fixing element 110 is a bracket partially surrounding a receiving profile, which can be one of the longitudinal profiles 93, 94 or another profile 91, 92. Several holes 94a in the profile (see FIG. 6C) can receive pins or similar retaining inwardly protruding parts of the bracket, for example for an anti-sliding effect.

[0190] The brackets may be elastically deformable, for example, allowing removal of the fixing element 110 from the frame 15, by moving the arms of the bracket further apart. The brackets may also, in some options, be hinged. Thus, the tubing holder formed by the fixing means MF1, MF2 can be removed once the line is in use (the inlet line is no longer useful after the fill line has been disconnected).

[0191] The fixing element 110 here has a C- or U-shape in cross section, thus forming a bracket. The bracket defines an internal space or recess for accommodating a portion of the profile 94. Referring to FIG. 10 or FIG. 6E, the tube T can be a filling line connected to the pouch 2 for the purpose of the filling operation. For example, the tube T is received and held / positioned by the fixing means MF1, MF2 while remaining connected to the pouch 2 via a connector (permanent connection). Another connector (which is a sterile connector) can be provided with two complementary parts C11 at the other end of the tube (opposite the permanent connection). This allows for aseptic disconnection of the tubing in a biopharmaceutical manufacturing process.

[0192] The fixing element 110 may also include a clamping part 113, which forms a receiving cavity bounded by a concave inner surface. A portion of the tubing outer wall, which may be cylindrical, may be inserted and fitted into this receiving cavity (in the same manner as the blocking groove BG). The portions of the tube T received in one or both cavities of the fixing element 110 or in the blocking groove BG, respectively, may extend completely above the plane XY when the protective body part and the pouch 2 extend horizontally.

[0193] The further the flexible tube T is from the periphery of the system 1, the lower the risk of accidentally handling and disconnecting this hose or tube T, for example during a transport step. However, this tube T now remains easily available to the operator.

[0194] The tubing holder can be an assembly for holding two tubes T so that they are symmetrically arranged with respect to the longitudinal direction X (i.e., the pouch longitudinal axis A). Each symmetrical part can hold one hose / tube T.

[0195] 4A, 6A and 10 respectively show solutions for horizontal storage, it will be understood that the pouches 2 can also be stored vertically or along any suitable direction by virtue of the storage unit 10. A sliding structure can be used to allow the protected pouches (in a frozen state) to be carried by an annular frame or similar holding means that can extend vertically for storage purposes.

[0196] Pouch filling Several flexible pouches 2 can be filled and protected within the system 1. As shown in FIG. 10, a shelf can be formed by several stacked systems 1. The flexible pouches 2 within these systems 1 can be frozen, thawed, filled, or emptied simultaneously as they are stored on such a type of shell device. When the flexible pouch 2 is stored, the biopharmaceutical fluid / composition Q can be frozen or thawed. When the flexible pouch 2 is shipped, in most cases the biopharmaceutical composition Q is frozen, even though the biopharmaceutical fluid can be thawed as well.

[0197] The flexible pouch 2 is allowed to expand during the filling operation, meaning that the perimeter of the two main walls W1, W2, as considered to be in the pouch plane (corresponding to the protective body reference plane P), is reduced due to inward movement of the different sides (also known as the retraction stroke). Here, in a horizontal configuration of the system 1 as shown in Figure 4A or 6A, the four pouch sides can be displaced inward due to vertical expansion (along the Z axis).

[0198] 1-3, due to the lower flexibility of the material of the two plates 12A, 12B (optionally provided with outer ribs), pouch expansion is limited and controlled by the protective body portion 12, 112. The protective body portion 12, 112, 212 is made from a freeze-resistant polyester or copolyester material that is not brittle at about 25°F or -4°C. This material is, for example, PET or a robust copolyester of the TRITAN™ type.

[0199] Referring to Figures 3, 5A and 7A-7B, a support structure (typically underlying in the form of a frame 15) is capable of receiving and guiding positioning members PM, PM' so that the system 1 is suitable for managing the contraction of the protective body portion 12, 112, 212 containing the pouch 2 during the filling operation.

[0200] The contraction of the protective body part is managed through the positioning members PM, PM' acting as stops and the rigid covering part, here formed as elongated profiles 91, 92, 93, 94 maintained / fastened in a frame structure. The four corners are provided in the frame 15, possibly using specific front and rear corner sections 15 made separately from the profiles 91, 92, 93, 94, - the profiles 93, 94 remain parallel to the longitudinal axis X1 and cannot move; and - that the profiles 91, 92 remain perpendicular to the longitudinal axis X1 We guarantee this.

[0201] Since the stopper-like positioning members PM are attached to the edges at the peripheral margin 80 and are encapsulated or sustained in an annular housing contained in the frame 15, adding a gap between the sliding positioning members PM and the abutment surfaces AB1, AB2 allows these sliding positioning members PM to move in one direction, more precisely: - in the X direction with respect to the stopper / positioning member PM located on the long side of the peripheral margin 80; in the Y direction for each of the stopper / positioning members PM, PM' which are positioned on the short sides of the peripheral margin 80.

[0202] This two-axis freedom of movement allows the protective body portion 12, 112, 212 to contract within the protective body portion reference plane P and to expand vertically, allowing the pouch 2 to be filled to the required volume.

[0203] 11A or 4D, 4G and 12A, positioning members PM are shown that are constructed identically, for example with a lower part LP and an upper part UP that are fastened to one another (respectively below and above the peripheral margin 80). Due to differences in position or thanks to the attachment of abutting contact parts, some of the positioning members PM can then be differentiated and provided with specific front surfaces BS, possibly distributed so as to be integral with the lower part LP and upper part UP of a given positioning member PM differentiated as an early stop.

[0204] 4D shows half of a positioning member PM, which may be the upper part shown in FIG. 4C. Here, the positioning member PM is made up of two identical halves, one forming the upper part UP and the other forming the lower part LP. Each positioning member PM is elongated and extends between two opposite ends 9c, 9d. In the assembled configuration, the positioning member PM has two opposite sides 9a, 9b (here, horizontal faces) that are generally parallel to the protective body part 12, one of which corresponds to or includes face F9. - Surface F9 is equipped with insert parts (IP1, CF1), face F9 faces towards the peripheral margin 80 so as to have insert parts (IP1, CF1) that match (here exactly match) the profile of some elements (here four relief elements) of the fastening system 18 contained within the margin 80.

[0205] Moreover, the positioning member PM has two parallel elongated sides which, in the assembled state, extend perpendicularly to the reference plane P. The inner face of the positioning member PM is one of these two parallel elongated sides and is suitable for engagement on one or more abutment surfaces AB1, AB2 provided in the frame structure, such engagement being a function of the filling level of the pouch 2 clamped by the plates 12A, 12B.

[0206] In some options, the positioning member PM, PM' has one or two parts LP, UP, LP', UP' that can be inserted onto the peripheral margin 80. Each part has an inner face facing the abutment surface AB1 or AB2 and an outer face. With respect to the insert parts provided in the contact surface that contacts the protective body part 12, one of the inner and outer faces is offset more than the other face by a face DF9. Such an offset along the radial direction (corresponding to the contraction direction) is of interest in order to have a part of the positioning member PM, PM' that can slide more than the other positioning member. This allows for contraction management, for example, to have the effect shown diagrammatically in Figures 9A-9B (a higher storage level in the middle area of the protective body part 12, thus minimizing the bulge size in the middle section MS of the pouch 2).

[0207] 4G, it can be seen that the asymmetric piece structure of parts UP, LP can be advantageous to have an efficient insert or similar attachment on peripheral margin 80 and also to have the ability to position positioning member PM closer to or farther from inner section 15a (where abutment surfaces AB1, AB2 are formed) of frame 15. Compared to the assembly of FIG. 8, in which the positioning member parts (typically having attachment features for securing plate 12A to plate 12B) must be disposed in irregular predetermined locations, the configuration shown with offset face DF9 also makes it possible to have peripheral margin 80 without through-holes and / or less flexibility for varying the arrangement of positioning member PM.

[0208] The offset surface DF9 is here provided with a relief or ribbed portion 90, but any other surface may be obtained having a surface DF9 that is further from the insert area than the opposite surface. The offset or shift distance SD in such asymmetric pieces can be greater than or equal to 2 mm or 3 mm, and in some cases greater than or equal to about 6 mm or 7 mm (typically less than 10 mm).

[0209] In the embodiment of Figures 4F-4G, near the corner section 15c, the respective offset surfaces DF9 are external surfaces of the lower and upper parts LP, UP. In contrast, at an intermediate distance between the rear and front corner sections along the same frame side, at least one or two positioning members are in a different position, rotated 180° around the Z direction, compared to the other positioning members PM attached to the same margin portion 8a or 8b. Such a configuration can be obtained in two margin portions 8a, 8b, where only the middle part 82 of the protective body portion 12 is interleaved by the positioning members PM, and the internal surface of the positioning members PM is the offset surface DF9 to form an early stop during the pouch filling operation.

[0210] 4E, the positioning member PM′ surrounding a portion of the port 24 can also be preferably elongated so as to have substantially the same length as the positioning member PM in the exemplary embodiment. This particular centrally open positioning member PM′ also has halves (preferably identical halves) extending between two opposite ends 9 c, 9 d, respectively, and here provided with offset faces having a relief 90, which when facing radially outward, allows for a larger retraction stroke (within the profile cavity CP) compared to some of the positioning members PM having offset faces DF9 facing radially inward.

[0211] As far as the long sides of the peripheral margin are concerned, the stops can be distributed symmetrically, while the distribution on the short sides can be either symmetric or asymmetric. Figure 11A illustrates an option with three forward surfaces BS' distributed among three corresponding positioning members PM located on two opposite short sides of the peripheral margin 80. Inside the forward profile 92, two early stops can be formed near the corner regions CR and away from the central region where the openings 80a for the ports 24 are provided, although other distributions are also possible.

[0212] In some variations, the mounting device or system 18 includes one or more cross members configured to maintain the positioning members PM in the assembled state. Such cross members can include an insert piece IP (FIG. 5A) and an associated fastening lock (e.g., a mechanical lock such as a nut or bolt). Referring to FIGS. 5A-5B, such cross members exert a holding effect through holes 18o that match a pair of slots or apertures 102 provided in the plates 12A, 12B.

[0213] The cross member is part of the attachment means, which can be placed in a locked state. In the locked state, the cross member cannot move or slide along the Z direction through the protective body portion 12, 112, 212 to prevent vertical separation of the parts UP, LP of the positioning member PM. Referring to FIG. 7A, the upper part UP and the lower part LP typically clamp the peripheral margin 80 of the pouch 2 in an area outside the clamping. FIG. 7A illustrates the initial position of the positioning member PM in the empty state of the pouch 2. A gap is provided between each of the parts UP, LP and the inner side or inner section 15a of the corresponding receiving profile to allow for contraction. A gap between the outer surface of the positioning member PM and the outer section 15b may be provided here. When the protrusion or relief 90 faces outward (which is the case, for example, for members PM arranged away from the intermediate parts of the respective margin portions 8a, 8b), there is initially a higher gap between the inner section 15a and the inner surface of the positioning member PM, thus allowing a larger sliding stroke and a larger angle between the sheets 21, 22 of the pouch 2.

[0214] 7B, such a higher sliding stroke can also be obtained by using a relief 90' that just passes through the inner section opening (elongated opening O). Thus, the shift distance SD' can be obtained without having the relief 90' abutting the abutment surfaces AB1, AB2. More generally, the manner in which asymmetric features are integrated into the positioning member is not limited to the example shown.

[0215] 7B, it can be seen that a biopharmaceutical composition Q has been introduced into the flexible pouch 2 and each of the positioning members PM may, in some cases, be displaced inwardly in a final position in which the positioning members PM abut inwardly against abutting rim portions BS1, BS2 of the frame profile. Each of the parts UP and LP may include a forward protruding portion or relief 90′, which engages / extends through the elongated opening O of the profile in the filled configuration of the pouch 2.

[0216] The forward projections or reliefs 90, 90' of these parts UP, LP, respectively, can have inclined surfaces that reach the pressing surfaces in contact with the protective body part 2, so as to form inwardly opening V-shaped cross-section grooves GS (distributed on both sides of the body part peripheral margin 80). This groove GS can guide the expansion of the protective body part near the peripheral margin 80 in order to prevent direct contact of the surfaces S, S' with the frame 15 (and therefore any contact with any profile edge / surface). This is of interest to protect the protective body part material, since the profiles 91, 92, 93, 94 are typically made of a harder material (e.g. steel, metal or hard plastic).

[0217] 1, the two plates 12A, 12B are sufficiently flexible to allow the protective body portion 12 to have a localized thickness at or near the central area that is greater than that in the surrounding areas. Thus, when the biopharmaceutical fluid is frozen, the storage area / receiving portion 2r or useful part of the flexible pouch 2 (i.e., the inner area relative to the peripheral seal J) can bend slightly. Thus, the longitudinal dimension X of the protective body portion 12 is slightly reduced. In this case, the biopharmaceutical fluid is slightly constrained by the two plates 12A, 12B.

[0218] Draining the pouch 6D (see also FIG. 11A or 12A), the positioning members PM can be assembled around the entire periphery defined by the peripheral margin 80, such that more than 80% of the periphery of the peripheral margin 80 is covered by the positioning members PM, PM′, where the spacing between the positioning members PM is small, possibly less than 5 cm or less than 5% of the length of the protective body part, other than at the angle of the protective body part and / or other than at the openings 91 a contained in the profile 91 matching the openings 80 a.

[0219] With such an arrangement, the useful volume accommodated by the protective body part under the covering portion 8 has limited deformation (insignificant wave-like deformation). Moreover, such sliding is performed during filling and during draining. After draining, the slider / sliding positioning member PM, PM' can slide back without interference from the frame 15, with the protective body part regaining its maximum perimeter (i.e., initial perimeter).

[0220] To prevent the formation of undesired waves or similar reliefs on the outer surfaces S, S', some sliders 41 are configured to allow a belt effect in the intermediate region MR, as will be explained in more detail below (see, for example, FIG. 9A). After drainage, the absence of waves is advantageous because the plates 12A, 12B cannot get caught on the frame 15 at the inner side openings. This minimizes the residual volume (hold-up volume) after the drainage operation.

[0221] Moreover, in cases where the pouch 2 is not filled to its full capacity (e.g. filled to 75 L for a 100 L pouch), in some options optimization of drain discharge can be obtained using biasing members BM, BM', which act to have an appropriate tension on the plates 12A, 12B and thus prevent undesirable waves or similar noticeable irregularities / reliefs on the outer surfaces S, S'.

[0222] 6B-6C, the biasing member BM, BM' is configured to exert a return action to displace the slider / slidable positioning member PM outward toward a first (initial) position, which is the default position in the unfilled / emptied state of the pouch 2. FIG. 6B illustrates an example of a positioning member PM provided with a contact surface or part made of foam material and / or silicone (possibly with a lattice or extruded silicone). This can be any suitable compressible material with shape memory or sufficient elasticity. Such contact part (here in front of the positioning member PM) pulls back a corresponding region of the peripheral margin 80.

[0223] When having a positioning member provided with an upper part UP and a lower part LP separated from the upper part UP by a peripheral margin 80, the biasing member BM made of a compressible material can also be divided into two parts (upper biasing part UBM and lower biasing part LBM), which extend into a cavity CP or similar gap between the front surface of the upper part UP or the front surface of the lower part LP, respectively, and the abutment surfaces AB1, AB2.

[0224] A biasing member or similar piece tensions the plastic plates 12A, 12B, compressing and maintaining the pouch even when the pouch is filled well below its capacity. This return force solution is typically: - used to maintain contact (as continuous as possible) between the pouch 2 and the plates 12A, 12B; - used to tension the plates 12A, 12B to protect the pouch (by reducing the freedom of movement of the pouch 2) after partial draining (aliquoting) or when the pouch is underfilled; - Used to protect underfilled pouches from eventual impact between the stopper / locating member PM, PM' and the frame 15 caused by handling or shipping stresses.

[0225] Naturally, the filling of the pouch 2 still causes a gradual deformation of the protective body portion 12, 112, 212, generating a pulling action (in the protective body portion reference plane P) to pull the slider inwards, which pulling action increases with the level of filling of the pouch 2 and opposes the return force / action of the biasing members BM, BM'.

[0226] In the embodiment of Figure 6C, biasing member BM' also provides one or more contact parts that are in contact with abutment surfaces AB1, AB2 in the second position for the filled state of pouch 2. In this example, leaf springs or similar spring parts are provided to tension plastic plates 12A, 12b to maintain pouch 2 in compression. Each biasing member BM' is configured to exert a return action to displace slider / slidable positioning member PM outwardly towards the first position in the unfilled state of the pouch.

[0227] The biasing member BM′ may optionally be provided with two branches 75 a, 75 b, which here form contact ends above and below the margin portion 80 against the corresponding abutment surfaces AB1, AB2. The biasing member BM′ may optionally be a single piece 75 forming a leaf spring. This biasing member BM′ may have a fastening part (possibly not deformed during use) that is fastened to the positioning member PM via one or more insert pins 78. In some options, the positioning member BM′ may clamp the associated positioning member PM using, for example, a bracket as the fastening part, while one or more deformable parts 76 are provided as extensions attached to the bracket. Each deformable part may be spaced (partially or entirely) from the positioning member PM and protrude forward relative to the positioning member front face.

[0228] 5A-5B, several hooks HK may be provided with handle parts for manipulating and (outwardly) pulling the positioning member PM. Here, the hooks HK are preferably attached to the positioning member PM, directly or indirectly, on the side opposite the abutment surfaces AB1, AB2. These hooks HK provide access to the edges of the protective body part, allowing the user to manually pull these edges and, if required, completely drain the pouch 2. Such a solution may be provided with or without the integration of biasing members BM, BM'.

[0229] More generally, the frame 15 of the system 1 may be provided with any suitable tensioning element. In the illustrated embodiment, the tensioning element includes a guide member T1 that is displaceable transversely relative to the two longitudinal support parts and is connected to a portion of the peripheral margin 80. Several windows O9 may be provided in at least one outer surface of the frame 15 to allow the tensioning member guide member T1 to be displaced from the cavity CP toward the outside of the frame. The tensioning element is configured to pull all or part of the peripheral margin 80 outward, here from the position shown in FIG. 5A to the position shown in FIG. 5B, when the tensioning element is displaced from a retracted position to an extended position (with the operating part of the tensioning member spaced apart from the frame 15, as shown in FIG. 5B).

[0230] Details of an Exemplary Embodiment for Controlling Pouch Expansion In the embodiment of Figure 8, the plate dimensional reduction (when considered in the XY plane) is obtained by the profile of the retraction stroke, and such reduction is adjusted differently depending on the longitudinal position of several positioning members PM that locally prevent or limit such dimensional reduction in order to control the retraction stroke.

[0231] Here, the positioning members PM (which are fixed to the peripheral margin 80 as shown in Figures 7A-7B) are distributed longitudinally, some of them being configured to limit the retraction stroke of the longitudinal sides of the protective body part by a stopping effect resulting from the engagement of the positioning members PM with the inner surfaces of the abutment rim parts BS1, BS2.

[0232] All or part of the positioning member PM are stops for providing stroke limits between the stops 41, 41', 42 and the abutment surfaces AB1, AB2 contained in the frame 15 of the holding and sustaining assembly HR. Referring to Figures 8 and 9A, the stops 41, 41' located at or near the mid-section MS of the pouch 2 are involved in creating a belt effect. In some embodiments, such a belt effect separates two abdomens or bulges B1, B2.

[0233] 8 and 9A-9B, the positioning members can act as stoppers 41 or 41' only in the two middle parts 82 of the protective body part 12. As a result, the pouch 2 covered by the containment protective body part 12, 112 or 212 cannot form a single belly or bulge in the middle, since the stroke is allowed in the area closer to the corner area CR (here, in the end part 81).

[0234] Moreover, the optional ribs R1, R2, R2', R3, R4 prevent the plate outer surfaces S, S' from forming fold lines or hollows in the corner regions that would limit successful filling of the biopharmaceutical composition Q. Such ribs, possibly with regions or portions of lower height (e.g., only at the diagonals DL1, DL2, since the guide and accordion-like effects are already obtained along the four sides of the rectangular-shaped protective body portion 12, 112), may help to expand the protective body portion 12, 112 from the inside without creating hollows or improper fold lines that would be detrimental to filling in the corner regions CR.

[0235] It will be appreciated that at a given filling level, the pouch corners and protective body corners can continue to move inward during the filling operation while the middle part 82 is blocked by the stops 41, 41'. In the corner regions CR, the retraction stroke is longer than that of the middle part, allowing at least the same liquid volume to be stored as in the absence of belly / bulging persistence.

[0236] Still referring to Figure 8, the stops 41, 41', 42 can be in place to form a positioning member PM, where only the stops 41, 41' positioned away from the end sides 120a, 120b have a relatively closer distance to the central symmetry plane of the protective body part 12 compared to the distance for stop 42. In such an option shown in Figure 8, such stops 41, 41', 42 follow the displacement (contraction) of the peripheral margin 80.

[0237] It can also be observed that the positioning members PM of Figures 4D, 4F-4G and 12A can also include such stops, which correspond to a configuration with an inwardly facing shift surface DF9, such that a similar intermediate part 82 can be provided with a positioning member that is slightly further from the long edge of the plate, as is the case in the example of Figure 8. Figure 4G also shows that the first stop 41 is formed by a member that extends less outward along the Y direction, while the second stop 42 is formed by another member PM, PM'.

[0238] During the filling operation, the stops 41, 41' provided in the intermediate parts 82 of the longitudinal margin portions 8a, 8b are (first) shifted inwards due to the arrangement of the mounting system 18 and / or due to the asymmetrical arrangement, and since the abutment surfaces AB1, AB2 are aligned parallel to the X direction, these stops 41, 41' come into abutment against the abutment surfaces AB1, AB2 well before the stops 42 adjacent / facing the corresponding corner regions CR. A belly-holding effect in the intermediate part of the protective body part 12, 112 is obtained.

[0239] In an option, ribs R1, R2, R3, R4 are provided in the plates 12A, 12B, possibly with corner ribs C1, C2 having a height profile that decreases towards the intersection area with the diagonals DL1, DL2. In such an option, the continuation effect (a bulging effect that decreases in the intermediate area MR close to the center C) is completed by a regular expansion of the area around the panel PP or PP1, PP2, preventing the undesired formation of pronounced fold lines.

[0240] Of course, Figure 8 is merely an exemplary embodiment for managing shrinkage of plates 12A, 12B. More generally, protective body portion 12 may be fitted to clamp flexible pouch 2 and received / held within the gap of any suitable retaining and sustaining assembly HR, which is rigid and defines the outer perimeter of system 1. Depending on the level of fill of pouch 2 clamped by plates 12A, 12B, protective body portion 12 may include one or more areas of maximum thickness. To accommodate this thickness variation, retaining and sustaining assembly HR may be annular in shape.

[0241] One or more bulges / bellies B1, B2 as illustrated in Figures 9A-9B may be formed due to expansion control and early stopping effect in the intermediate part (e.g., due to early blocking stoppers 41 and / or 41'), causing the intermediate section MS to move much less compared to the complementary sections covered by parts of the protective body part 12 near the first and second end sides 120a, 120b.

[0242] More generally, any configuration may be provided with positioning members that can form stops away from the corner regions CR, so that a higher restraining effect can be obtained in the center of the pouch 2, as illustrated in particular in Figures 9A-9B. This is of interest for managing the freeze / thaw behavior of the biopharmaceutical material stored in the pouch 2. It is also of interest for better stacking systems such as those illustrated in Figures 4A and 6A, with greater compactness (less vertical space between two adjacent storage units 10), thus providing the opportunity to store more pouches 2 in the freezing chamber.

[0243] The dashed lines in Fig. 9B show the type of abdomen that is usually obtained when also allowing a large stroke in the respective area of the peripheral margin 80. It is therefore of interest to limit or prevent the displacement of the middle parts of the protective body part 12, 112, 212, so as to limit the accumulated mass (of significant thickness) that may be difficult to unfreeze.

[0244] FIG. 9A shows that the frame 15 or any kind of retaining part of the assembly HR is suitable to allow the protective body part 12, 112, 212 to change its conformation (with a decrease in body width and body length) and thus to allow a reduction in: - The width of the pouch 2 (w' < w, where w' is the pouch width in the filled state as compared to the pouch width w in the empty state), and, - The length of the pouch 2 (L' < L, where L' is the pouch length in the filled state as compared to the pouch length L in the empty state).

[0245] In some variants, the positioning member PM can be positioned and held stationary in the through slots, for example, by being fixed to or being integral with a rigid frame 15 or a similar holding and sustaining assembly. The slots in the protective body part can be of a larger size only near the end side parts 120a, 120b, and thus allow for a larger contraction only in the corner region CR, preventing the formation of an overly large bulge near the center C (due to the abdominal effect / sustain in the intermediate part when the positioning member is an early stopping member).

[0246] The holding and sustaining assembly HR can include at least three positioning members PM distributed at each of the longitudinal side parts 120c, 120d, and typically one or two central stoppers 41 correspond to the positioning members PM arranged away from the corner region CR.

[0247] In addition to or independently of having such an abdominal sustaining effect, at least one of each system or of the systems in a stack of systems can be provided with a sample unit SU including a bag 2' in which a small amount representative of the biopharmaceutical composition Q can be stored. In the thawing stage, it may be of interest to have a sample unit SU that provides a small amount of the biopharmaceutical composition Q that has been subjected to the same treatment and the same freezing operation as the composition stored in the large - volume pouch 2. Being a small amount, it will heat up faster, thus accelerating the thawing operation for the contents of the sample unit SU.

[0248] The system 1 is well adapted for freezing, storing, and thawing biopharmaceutical materials contained within a simple concept flexible pouch 2. A storage unit 10 as described above is of interest for at least one of the following reasons: - to accommodate and handle very large volumes of pouches while minimizing one of the three dimensions of the storage unit 10 (along the Z direction); - obtaining a predictable expansion of the pouch while also having time gain for the defrosting and / or draining operations; - To prepare a biopharmaceutical composition Q with a high level of protection by means of an optimized bulk.

[0249] In embodiments with an adjustable positioning member PM, filling of the pouch 2 can be performed with controlled and limited expansion, such that expansion is limited in one or more areas where the fluid thickness would otherwise reach a maximum. The interior volume or cavity bounded by the main walls W1, W2 is expanded with the prevention of free expansion in the intermediate areas of these walls W1, W2. In particular, expansion can be limited along one or more belt lines BL joining two intermediate parts 82, as illustrated in FIG. 9A.

[0250] Such a depression along the belt line BL, due to a low or non-existent contraction stroke in the intermediate part 82, typically generates at least one recess in the pouch 2 when filled, and in the storage configuration of the storage unit 10, at least one recess is thus generated in the filled pouch 2 between the two bulges B1, B2. This allows a generally equal distribution of the fluid, since a more uniform thickness distribution is obtained without reducing the capacity of the pouch 2.

[0251] The pouch 2 and protective body portion 12 can be exposed to temperatures of about -70°C or below to freeze the biopharmaceutical fluid / composition Q. The annular shape of the frame 15 of the holding and sustaining assembly HR is of interest to provide a recessed area through which cold air can circulate and flow between the systems 1 (even when the systems 1 are stacked). However, other shapes and structures can be used to form the holding and sustaining assembly for controlled expansion, so as to eliminate or reduce the formation of excessive protrusions during freezing.

[0252] Although the present invention has been described in connection with preferred embodiments, it is to be understood that these embodiments are merely exemplary and that the present invention is not limited thereto.

[0253] Of course, the pouch 2 of the present invention is in no way limited to a pouch having four sides and / or a pouch that is wider than the width. The pouch 2 can have other shapes provided with two generally parallel sides covered by a pair of plates 12A, 12B or similar protective body comprising two flat portions. While each plate 12A or 12B is illustrated as a one-piece element, the option of combining two or more flat containment pieces that can limit the expansion of the pouch 2 while being more or less displaceable for adjusting the retraction stroke is also available.

[0254] It will be understood by those skilled in the art that other variations and modifications can be readily made within the scope of the invention as claimed.

[0255] Any reference signs in the following claims should not be construed as limiting the claim. It will be clear that the use of the verb "to comprise" and its conjugations does not exclude the presence of any other elements other than those defined in any claim. The word "a" or "an" preceding an element does not exclude the presence of a plurality of such elements. [Explanation of symbols]

[0256] 1. Freeze / Thaw Containment System 2 flexible pouches 2' Bag 2r Reception Department 4 first transverse rib portion 6 second transverse rib portion 8 Covered part 8a, 8b Margin area 9a, 9b Side 9c, 9d ends 10 Storage Units 12 Protective body 12A Lower Plate 12B Upper Plate 15 Rectangular Frame 15a inner section 15b outer section 15c corner parts 15d extension 17 Connector 18 Mounting systems, mounting devices 18a First element: snap button 18b The second element: snap buttons 18o hole 21, 22 seats 24 ports, forward ports 31 Longitudinal support parts, longitudinal covering parts, protective parts 32 Longitudinal covering parts, protective parts 41 Early Stopper 41', 42 late stopper 75 single pieces 75a, 75b Branch 76 transformable parts 78 Insertion Pin 80 Peripheral Margin 80a opening 81 End parts 82 Intermediate parts 83, 84, 85, 86 Ribs 90 Ribbed parts, protrusions and reliefs 90' Relief 91, 92, 93, 94 frame profiles 91a opening 92a, 92b pieces, parts 92o opening 94a Hole 102 Aperture 110 Fixed Elements 112 Protective body 113 Clamp parts 115 Lower foot 116 Upper foot 120a first end side, transverse side 120b second end side, transverse side 120c, 120d longitudinal side 130 Casing 132, 133, 134 Fastening elements 146, 147, 148 Fastening members 160 Anchor fixing relief 162 Abutting end 200 storage parts 212 Protective body 800 ribs A Pouch longitudinal axis AB1, AB2 contact surfaces B1, B2 bulge B12 First boss part B12' Second boss part BG Blocking groove BL Belt Line BM, BM' biasing member BS, BS' anterior surface BS1, BS2 Rim, contact part C center C1, C2, C1', C2' corner ribs C9 Clamping member CF1 cavity CP Cavity CR Corner Area Cli Complementary Parts DF9 Offset faces, shift faces DL1, DL2 Virtual diagonals E1 end E2 end F9 side G1, G2 groove G9 groove GS groove HK Hook HP1 Lower Section HP2 Lower Section HR Retention and Sustainment Assembly IP insert piece IP1 Insert part, insert protrusion IP' insert protrusion J Peripheral seal L Pouch length when empty L' Pouch length in filled state L8 length LBM lower energizing part LP, LP' lower parts LS1, LS2 longitudinal side MF1, MF2 fixing means MR intermediate area MS Mid Section O opening O9 window OP1, OP2 opening OPC center opening P Protective body reference plane PM, PM' positioning member PP central panel PP1 Panel part, panel PP2 Panel part, panel Q Biopharmaceutical compositions, biopharmaceutical fluids R1, R2, R2', R3, R4 ribs Outer relief for RS clamp S Upper surface, outer surface, second surface S' lower surface, first surface SD, SD' shift distance SU Sample Unit T Hose / Tube T1 Guide member UBM upper energizing part UP, UP' upper part w Pouch width when empty w' Pouch width in filled state W1, W2 Main walls W8 Maximum width of positioning member PM X-axis, longitudinal direction X1 Longitudinal axis XY principal plane Y axis, transverse Z vertical axis

Claims

1. 1. A system for preparing a biopharmaceutical composition, the system being for use in freezing, storing, and thawing the biopharmaceutical composition contained in a flexible pouch, the system comprising: - a protective body including two plates for protecting the pouch, the protective body including a longitudinal axis and four sides, the four sides including two longitudinal sides extending parallel to the longitudinal axis and two other sides; - a mounting system for fastening the two plates, wherein the protective body part includes a peripheral margin extending annularly in a protective body part reference plane, the peripheral margin being provided with at least one opening capable of receiving at least one port of the pouch; a plurality of positioning members fixed to or formed on said peripheral margin; a frame extending around a hollow space into which the pouch extends, the frame being provided with two longitudinal support profiles separate from the positioning member; and Including, the frame includes abutment surfaces contained and distributed among the two longitudinal support profiles, and the plurality of positioning members connect the peripheral margins to the frame such that the frame holds and supports the protective body portion and the pouch sandwiched between the two plates that restrain the pouch; sliders forming positioning members of the plurality of positioning members are slidably mounted in the two longitudinal support profiles, in particular in the profile cavities (CP), and are movable between a first position and a second position along a direction transverse to the longitudinal axis, - in the first position, in an unfilled state of the pouch, the slider is pushed outward by the protective body part or maintained away from the abutment surface, allowing the slider to be displaced inward; - in said second position, in a filled state of the pouch, said sliders are engaged against one of said abutment surfaces, respectively; the abutment surfaces of the two longitudinal support profiles are contained in an abutment element extending transversely to the protective body reference plane, wherein each of the abutment members is configured to separate the hollow space from a cavity that is a profile cavity (CP).

2. 10. The system of claim 1, wherein filling the pouch causes a conformational change in the protective body portion with contraction of the protective body portion in the protective body portion reference plane, the contraction of the protective body portion resulting from passage of the slider from the first position to the second position.

3. the positioning member is distinct and separate from the pouch and the plate, and the positioning member is configured to protrude from at least one of the lower surface and the upper surface of the protective body portion at the peripheral margin, respectively; The system of claim 1.

4. The system of claim 3 , wherein the positioning member is provided with one or more insert parts for removably inserting onto the peripheral margin.

5. 5. The system of claim 4, wherein the positioning member includes a lower part and an upper part, the lower part and the upper part being two separate pieces configured to clamp the protective body portion in the area of the peripheral margin.

6. The positioning member includes a lower part and an upper part, each of which is two separate pieces configured to clamp the protective body portion at a clamping region of the peripheral margin, each clamping region comprising: - elongated parallel to the edge of the protective body, 10. The system of claim 1, wherein the positioning member is at least four times longer than its maximum width.

7. the slider is part of the mounting system; 4. The system of claim 3, wherein the slider supports or includes an insert piece engaged with the protective body portion through a thickness of the peripheral margin.

8. The system of claim 1 , wherein the positioning members are distributed at different longitudinal locations along the longitudinal axis.

9. 2. The system of claim 1, wherein the two longitudinal support profiles are provided with a U-shaped or C-shaped cross section and are each configured to define one of the profile cavities (CP), which is an internal cavity.

10. 10. The system of claim 1, wherein the two longitudinal support profiles are rigid and made of aluminum or alloy pieces.

11. The system described in claim 10, wherein the frame is rectangular by being assembled from four rigid profiles including the two longitudinal support profiles.

12. the frame is rigid and includes two transverse support profiles separate from the positioning members; Each of the two transverse support profiles houses an additional slider, the additional slider comprising: forming a positioning member among the plurality of positioning members, 12. The system according to claim 11, wherein the transverse support profiles are each slidably mounted in a corresponding transverse support profile and are movable along the longitudinal axis.

13. the frame has a rectangular shape thanks to the two longitudinal support profiles and the transverse support profile, the frame includes additional abutment surfaces contained and distributed in the two transverse support profiles, the additional sliders being movable along the longitudinal axis between a first position and a second position; - in the first position, in an unfilled state of the pouch, the additional slider is pushed outward by the protective body part or maintained away from the additional abutment surface, such that the additional slider can be displaced inward due to a conformational change of the protective body part; 13. The system of claim 12, wherein in the second position, in a filled state of the pouch, the sliders are engaged against respective ones of the additional abutment surfaces.

14. the protective body portion has a rectangular shape with four corner regions spaced from a middle region of the protective body portion; 13. The system of claim 12, wherein eight corner sliders, including four of the sliders and four of the additional sliders, are distributed at each end of the two longitudinal support profiles and at each end of the two transverse support profiles to increase contraction of the protective body portion in the protective body portion reference plane in each of the four corner regions during filling of the pouch.

15. the protective body portion has a rectangular shape with four corner regions spaced from a middle region of the protective body portion; 3. The system of claim 2, wherein the sliders are distributed at the ends of each of the two longitudinal support profiles so as to increase the contraction of the protective body in the protective body reference plane in at least one of the four corner regions.

16. the system further includes a biasing member configured to exert a return action to bias the slider outwardly toward the first position, the first position being a default position for an unfilled and emptied state of the pouch; 10. The system of claim 1, wherein filling of the pouch causes a gradual deformation of the protective body portion, generating a pulling action in the protective body portion reference plane to pull the slider inward, the pulling action increasing with the level of fill of the pouch and opposing the biasing action of the return member.

17. 2. The system of claim 1, wherein all or a portion of the slider is provided with a contact part that contacts the abutment surface in the second position, the contact part being a biasing member configured to exert a return action to displace the slider outward toward the first position, the first position being a default position in an unfilled and emptied state of the pouch.

18. the system includes a tension element, the tension element being displaceable transversely relative to the two longitudinal support profiles and connected to a portion of the peripheral margin; The system of claim 1 , wherein the tensioning element is configured to tension all or a portion of the peripheral margin outward when the tensioning element is displaced from a retracted position to an extended position.

19. 10. A method of assembling the system of claim 1, wherein the system is a protective system for storing and withstanding freezing and thawing of a biopharmaceutical composition contained in a pouch of a freeze / thaw containment system, the method comprising: - sandwiching the flexible pouch between two plates of a protective body part, optionally with covering portions distributed among the two plates to cover the flexible pouch, the protective body part being configured to protect the flexible pouch and comprising the two plates, the protective body part further having a longitudinal axis and comprising four sides, the four sides comprising two longitudinal sides extending parallel to the longitudinal axis and two other side sides; - using a mounting device for fastening the two plates, such that in the assembled state of the two plates, the protective body part includes a peripheral margin extending annularly around the covering portion in a protective body part reference plane, the peripheral margin comprising: - at least one opening for receiving at least one port of said flexible pouch; and a plurality of positioning members fixed to or formed on said peripheral margin; Steps and Including, In the assembled state of the two plates, a frame is mounted around the protective body by connecting two longitudinal support profiles, separate from the positioning members, to the peripheral margin, which, when connected to the peripheral margin, extend parallel to the longitudinal axis and form two opposite sides of the frame, delimiting profile cavities (CP) corresponding to each longitudinal support profile, and the positioning members connect the peripheral margin to the frame; The abutment surfaces are contained and distributed between the two longitudinal support profiles, and the frame is - the protective body part; the pouch being sandwiched between the two plates that restrain the pouch; and has become a sustained supporter of sliders forming positioning members of the plurality of positioning members are slidably mounted in corresponding profile cavities (CP) in the two longitudinal support profiles during mounting of the frame, and are movable between a first position and a second position along a direction transverse to the longitudinal axis; - in the first position, in an unfilled state of the pouch, the slider is pushed outward by the protective body part or maintained away from the abutment surface; - in the second position, in a filled state of the pouch, the sliders are engaged against one of the abutment surfaces, respectively.

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