Freezing / Thawing Containment System for a Flexible Bag Filled with a Biopharmaceutical Fluid, and Method of Assembling a Freezing / Thawing Containment System Using a Protective Body

Abstract

A freezing / thawing containment system is provided, which has a protective body and a flexible bag having a first capacity, and the flexible bag is protected by two plates of the protective body. The two plates are attached together at the peripheral boundary and form a rectangular protective body. The peripheral boundary is mounted in a fixed frame and allows inward displacement during filling of the bag, while the protective body extends substantially in a plane to sandwich and constrain the bag. One of the fixed frame and the protective body includes a fastening member for attaching a housing configured for storing a package bag so as to fasten the package bag parallel to the protective body. Two fasteners for cooperating with the fastening member are distributed around a package bag accommodation portion having a second capacity, and the second capacity is at least ten times lower than the first capacity. The same biopharmaceutical composition is accommodated in the bag and the package bag.

Description

Technical Field

[0001] The present invention generally relates to the protection of flexible bags specifically designed to contain biopharmaceutical fluids, and more broadly to systems for containing biopharmaceutical fluids. The present invention also relates to methods for manufacturing / assembling such systems, which are adapted to freeze and thaw biopharmaceutical fluids within the system. Biopharmaceutical fluids mean biotechnology-derived fluids, such as fluids derived from culture media, cell cultures, buffer solutions, artificial nutrient solutions, blood fractions, blood-derived components, or pharmaceutical fluids, or more broadly, fluids specifically designed for the medical field. Of course, the fluid may become solid or partially solid after freezing (usually at temperatures well below 0°C). Background Art

[0002] It is known to use flexible bags to contain biopharmaceutical fluids. Flexible bags can withstand low mechanical stresses without damage. Therefore, the risk of leakage is reduced. In addition, flexible bags are advantageous because they can be folded or laid flat when there is no biopharmaceutical fluid inside. Therefore, flexible bags occupy a small volume.

[0003] Flexible bags are typically designed to be disposable and contain biopharmaceutical fluids in volumes between 1 liter and 500 liters.

[0004] However, specifically, in order to fill flexible bags with fluid, for example, during shipment between several factory areas or from a fluid supplier to a customer who will use it, and for storage, the flexible bags must be protected, although the risk of leakage is small.

[0005] Document EP-2 322 442 discloses a container for a flexible bag. The container includes a lower part and an upper part, which are rigid and joined along a common edge and form a one-piece container. The container has a volume much larger than that of the flexible bag. Therefore, the container has an unusable volume. In addition, if the flexible bag is not held by a suitable positioning member provided in the container, the flexible bag may move inside the container, especially during shipment. Therefore, the risk of leakage increases.

[0006] Disposable polymer containers (hereinafter referred to as bags or sacks) have been successfully used for storing liquid biopharmaceuticals. Nowadays, it has been found that bags made of ethylene vinyl acetate (EVA) or low density polyethylene (LDPE) are suitable for storing and shipping biobulk items at ambient temperature or low temperature (2 °C to 8 °C). However, currently configured bags have problems in cryogenic applications. At low temperatures, the physical properties of the plastic material may change sufficiently to introduce brittleness, which will reduce the ability of the bag to absorb external forces, i.e., the ability to absorb shock without rupture. Additionally, ice volume expansion may cause significant mechanical stress, resulting in breakage of the bag, ports, pipes or connectors. It is well known that currently commercially available unprotected bags do not adequately protect cryogenic products.

[0007] To eliminate problems associated with bag breakage, Sartorius Stedim Biotech has developed the Celsius TM FFT concept (FFT means "Flexible Freezing and Thawing"), which combines a flexible bag with a semi-rigid protective shell. The main function of the protective shell is to absorb the stress generated from processing or handling conditions.

[0008] Document US 2018 / 125757 provides a protective body such that a flexible bag is sandwiched between two plates of the protective body, having a constraining effect. By combining a disposable flexible container wrapped by such a protective body and a protective shell, a freeze / thaw protection system can be obtained. However, uniform fluid distribution may be difficult because, in the filled state of the flexible container, a significant bulge (large swelling) forms in the middle. In the frozen state, ice expansion is thus relatively significant, and it takes more time to freeze this large mass in the middle of the internal volume of the bag.

[0009] Furthermore, for flexible containers with a large capacity, it would be meaningful to obtain / use a small volume of product contained in the bag without complex operations and without causing an increase in the volume of the system. Summary of the Invention

[0010] The object of the present invention is to provide a storage unit for obtaining a stable freeze / thaw containment and protection system that is effectively used to condition a large amount of biopharmaceutical material in a flexible bag with a flexible design (usually a 2D bag, which is then inflated in the filled state), while also allowing the use of all or part of the system as a backing / support part for enhanced functional integration, thereby making the system user-friendly.

[0011] For this purpose, an embodiment of the present invention provides a freeze / thaw containment system for containing a biopharmaceutical composition, comprising:

[0012] - A flexible bag having a first capacity, configured to contain a biopharmaceutical composition;

[0013] - A storage unit for freezing, storing, and thawing a biopharmaceutical composition contained in a flexible bag;

[0014] - A bag having a second capacity configured to contain a composition representing a biopharmaceutical composition, the second capacity being lower than the first capacity; and

[0015] - A housing defining an internal volume for receiving the bag in a filled state; wherein the storage unit includes:

[0016] - A protection body including two plates for protecting the flexible bag, the protection body including a longitudinal axis and having four sides, the four sides including two longitudinal sides extending parallel to the longitudinal axis and two other sides, the two other sides including a first end side and a second end side each perpendicular to the longitudinal axis, and

[0017] - An attachment device for clamping the two plates such that in the assembled state of the two plates, the protection body includes a peripheral boundary extending annularly in a protection body reference plane,

[0018] wherein the system further includes a rigid peripheral portion adjacent to or overlapping the peripheral boundary, the rigid peripheral portion having a mounting kit including three separate support members for supporting the protection body,

[0019] wherein in the assembled state:

[0020] - The protection body extends planar along the protection body reference plane in the emptied state of the flexible bag;

[0021] - The two plates respectively form (i.e., contain) a lower surface and an upper surface of the protection body, and at least one of the lower surface and the upper surface is an outer surface of the storage unit;

[0022] And wherein the housing includes at least two fastening elements that cooperate with a fastening member provided in / included in one of the mounting kit and the outer surface of the storage unit so as to fasten the housing along the storage unit, parallel to the protection body.

[0023] Thus, thanks to the sample unit or the bag, the sample is easily accessible. Thanks to the detachable fixing means, the bag can be easily attached to the protection body, and the housing generally extends along the outer surface of the storage unit and away from the middle portion of the protection body. This helps to improve tightness because when the flexible bag contains more than 50L or 75L, the thickness in such middle portions can be significantly greater compared to the thickness near the circumferential portion of the protection body. If desired, the bag can also remain attached to the protection body during transportation and during freezing / thawing operations without increasing the volume of the system in the filled state of the bag.

[0024] If the system has to be transported (possibly during freezing of the biopharmaceutical composition), the bag is advantageously protected by the housing. Thus, a sample unit is formed, providing a way to quickly analyze or test the composition, since the contents of the sachet thaw and are removed much faster at a uniform positive temperature than the contents of a bag with a relatively large capacity.

[0025] The bag and the storage unit are held together by a support member that defines all or part of the peripheral rigid portion.

[0026] Typically, the housing may extend above the outer surface of the storage unit formed by the upper plate of the two plates, and there may be no contact between the housing and the protection body. Optionally, all fastening members are provided in the mounting kit, preferably entirely above the protection body.

[0027] The storage unit may simultaneously have an expandable portion for expanding in the vertical direction (Z-direction) as the bag is filled, and a rigid sliding portion (fixed and not displaceable along the Z-direction) formed as an interface for insertion into a frame (usually an annular frame) or any similar portion surrounding the bag and cooperating with the peripheral boundary of the protection body. The expandable portion is constituted by the protection body (after the bag has expanded, typically having a restraining effect limiting such expansion in the vertical extension).

[0028] According to another alternative, the housing may be in contact (direct contact) with the outer surface of the storage unit, possibly without using an intermediate fastening device or an intermediate adhesive layer. One of the plates holds the housing such that the protection body serves as a backing assembly for the housing.

[0029] The sachet may be configured to contain the same composition as the composition in the flexible bag in order to form a sample.

[0030] The peripheral boundary may have at least one opening capable of receiving at least one port of the flexible bag. This helps to permit filling or emptying of the bag. The opening or port may be formed as, for example, a closable duct and may be provided between opposite portions of a welded joint where the two constituent sheets of the bag are joined. Such an opening may be meaningful to allow filling or emptying of the bag.

[0031] Optionally, two of the fastening members are integrally formed with two separate corner sections so as to be distributed over the frame surrounding the flexible bag. By such an arrangement, the sachet can be stored near the end portion of the system without the fastening members interfering with the position of the pipe that can be connected to the bag. Typically, the corner sections with the fastening members are remote from any open side of the peripheral boundary.

[0032] The peripheral part can be a frame with four corner sections interconnecting the frame outlines, and the peripheral boundary has only one open side located between two corner sections, the two corner sections being at the ends opposite to the ends of the two corner sections having fastening members for fastening to the housing.

[0033] According to an embodiment, the two plates are flexible enough to allow the protection body to have a greater thickness in the central region than in the circumferential region with respect to the protection body reference plane, the thickness being measured between the lower surface and the upper surface in a direction perpendicular to the protection body reference plane.

[0034] According to an embodiment, the flexible bag is directly sandwiched between two plates that constrain the flexible bag. The flexible bag is generally more flexible than the material of the protection body. The constraining effect helps the step of evacuating the flexible bag and is conducive to restricting the expansion of the fluid (vertical expansion when the protection body extends substantially horizontally such that the protection body reference plane extends substantially horizontally), especially during freezing.

[0035] The housing can be made of a plastic material that is more rigid than the plastic material of the flexible bag.

[0036] The two plates can constrain the flexible bag through corresponding covering portions extending between two boundary portions of the peripheral boundary.

[0037] Generally, the protection body is installed to cover two main opposite faces of the flexible bag and acts as an expansion guiding element adapted to expand in volume in an expanded state, such that the assembly composed of the protection body and the flexible bag covered by the protection body can fill the inner cavity defined by two protection portions or the gap defined between two protection portions without bulging more in the middle portion of the covering portion equidistant from the front and rear edges of the flexible bag and separating two other complementary portions having a longitudinal dimension the same as the longitudinal dimension determined for the middle portion (so the determined dimension is basically equal to one-third of the longitudinal dimension of the flexible bag because the covering portion has the same length as the flexible bag).

[0038] Optionally, a number of protection body through slots are provided and longitudinally distributed in each of the two opposite boundary portions.

[0039] The attachment means can interact with some of the protection body through slots or can be distributed at alternating positions relative to the protection body through slots.

[0040] In some embodiments, each of the two plates includes a convexity that, in the assembled state of the plates, defines to form the protection body, and a number of protection body convexities project in a first direction perpendicular to the protection body reference plane, thereby forming corresponding cavity openings in a second direction opposite to the first direction, and the convexities are longitudinally distributed in the peripheral boundary.

[0041] A plurality of protrusions may be provided in one of the two plates and engaged in the same number of corresponding cavities provided in the other of the two plates.

[0042] Independently of whether the bag is held by the protection body or by a frame or similar peripheral part (possibly via a housing), the system may include:

[0043] - A pipe connected to the flexible bag and configured to allow the flow of a liquid of a biopharmaceutical composition;

[0044] - A frame having four sides, forming a rigid peripheral part of the system and extending parallel to the protection body reference plane, at least two profiles included in the frame forming all or part of the four sides, the four sides preferably being formed by four profiles; and

[0045] - A pipe holder for holding the pipe, the pipe holder including at least one fixing element elastically mounted on one of the profiles and having a clamping part for holding the pipe.

[0046] Generally, the frame intersects the protection body reference plane and extends parallel to the protection body reference plane, and the frame is configured to directly or indirectly hold / support the protection body.

[0047] In some embodiments, the pipe forms a port of the flexible bag. In addition, the pipe holders may be distributed in two positions, having two separate and spaced fixing elements.

[0048] In some embodiments, at least one fixing element has one of the fastening parts (for the sample unit), the fastening part being adjacent to and / or superimposed on the clamping part.

[0049] In a variant, one of the four sides is suppressed such that the frame includes three profiles extending parallel to the protection body reference plane.

[0050] The fixing element may have a U-shaped or C-shaped section with an inner face for engaging three faces of a profile (receiving profile) that is part of the frame. The clamping part may be separated from the U-shaped or C-shaped section. The clamping part may be formed on the outer surface of the fixing element and may define a C-shaped receiving part that:

[0051] - Projects from the outer face of the bracket (fixing element),

[0052] - And / or faces a position opposite to the receiving profile.

[0053] In various embodiments of the system, one or more of the following treatments may also optionally be resorted to:

[0054] - The two plates are two parts.

[0055] - The two plates may have the same thickness of less than 2 mm, and each of the two plates has a density higher than 1.10 g / cm 3 and is made of a plastic material.

[0056] - The two plates are made of the same plastic material, preferably transparent or translucent

[0057] - The protective body is made of a freeze-resistant polyester or copolyester material that is not brittle at about 25°F or -4°C.

[0058] - The material of the protective body is PET.

[0059] - The material of the protective body is TRITAN (i.e., a copolyester compound called TRITAN TM which is a transparent amorphous thermoplastic material, usually composed of a combination of three monomers; some formulations of this material contain no additives, while others contain approximately or less than 10% additives).

[0060] - The material of the protective body is an amorphous copolyester composed of the following monomer combination: dimethyl terephthalate, 2,2,4,4-tetramethyl-1,3-cyclobutanediol, and 1,4-cyclohexanedimethanol.

[0061] - The protective body is directly joined by positioning members belonging to the attachment means so as to have a constricted profile at the circumference of the protective body, where there may be little or less constriction due to the direct joining of the positioning members in the intermediate region of the protective body at the boundary portion.

[0062] - The positioning members are distributed around the covering portion.

[0063] - The holding and retaining device has two separate protective parts that are interlocked by positioning members so that the protective body is clamped between the two protective parts and arranged in the gap defined by the two protective parts.

[0064] - The holding and retaining device includes a profile having, for example, a U-shaped or C-shaped section, each of which defines an internal cavity, and the positioning members are each arranged inside one of the corresponding cavities of the holding and retaining device so that the positioning members can selectively move inward depending on the stroke of the gap provided inside the cavity. When the adjacent surface belonging to a given positioning member abuts against the adjacent edge or adjacent surface of the profile accommodating the given positioning member, the positioning member acts as a stopper for restricting the expansion of the protective body.

[0065] - Each of the positioning members is joined by extending through at least one cutout or notch formed in one of the two boundary portions to extend through one of the two opposite boundary portions.

[0066] - The plane of the protection body intersects four boundary parts that are distributed in a rectangular shape and each contact two protection parts of the housing. The four boundary parts are arranged around the covering part, and two opposite boundary parts are part of this group of four boundary parts. In various embodiments, the system may have one or more of the following features:

[0067] - The fastening components are distributed in different (spaced-apart) zones.

[0068] - The fastening components are distributed in a first zone adjacent to a first side of two longitudinal sides of the protection body and in at least one second zone located away from the first side.

[0069] - The housing is fastened to the peripheral part (frame) in a detachable manner.

[0070] - The peripheral part includes a covering part that covers the peripheral boundary. The fastening components are formed as coupling parts of the mounting kit and are inserted between:

[0071] The contour of the peripheral part or a similar rigid component / support part (for supporting the protection body),

[0072] And the fastening elements of the housing.

[0073] - The rigid peripheral part is a frame having a top surface that extends above the protection body and a lower surface that extends below the protection body.

[0074] - The housing is fastened to the protection body in a detachable manner.

[0075] - The housing is fastened to the mounting kit in a detachable manner. The mounting kit extends around three sides of the flexible bag.

[0076] - The fastening components include two fastening components distributed on two longitudinal sides. The two fastening components extend completely above the protection body and away from the two other sides.

[0077] - The fastening components include at least one fastening component that is integrally formed with one of three separate support parts or with a corner section that interconnects two of the three separate support parts.

[0078] - The housing is attached to the outer surface of the storage unit by one or more snap buttons.

[0079] - The fastening components distributed on the frame including three separate support parts are configured for the interlocking of the housing.

[0080] - The fastening components provided on the outer surface of the storage unit are configured for the interlocking of the housing.

[0081] - The interlocking of the housing can be achieved by the positive locking of the convex protrusions in the corresponding recesses, such as snap buttons or similar protruding components for positive locking in the corresponding recesses.

[0082] - At least one of the convex protrusions can be formed / contained in one of the support components.

[0083] - At least one of the recesses can be formed / contained in one of the support components.

[0084] - At least one of the recesses can be directly formed / contained in one of the two plates, i.e., without any additional material of the constituent layer of the covering plate (if such a recess opens inwards, an external protruding component can be produced; conversely, if such a recess opens outwards, an external protruding component can be produced).

[0085] - The housing is usually fastened to the outer surface of the storage unit or to the mounting kit without any adhesive layer or any adhesive component.

[0086] - The housing is made of at least one part that is completely separated from the protection body and from the frame forming the rigid peripheral part, so that the housing can be completely removed from the protection body.

[0087] - The housing has a prismatic shape.

[0088] - The housing has a parallelepiped shape.

[0089] - The housing has a housing frame that defines a housing opening for accessing the internal volume of the housing.

[0090] - The housing has a cover configured to close the housing opening in a detachable manner (the cover partially defines the internal volume).

[0091] - In the protection body, compared to the longitudinal sides, the two other sides are the short sides of the protection body.

[0092] - The housing extends in a direction parallel to the two short sides of the storage unit (when fastened to the peripheral part and / or fastened to the protection body).

[0093] - Each of the two plates is a plate having a rectangular shape with four corners and two virtual diagonals each intersecting a pair of corner vertices of the four corners.

[0094] - The side wall of the housing intersects only one of the two virtual diagonals and is arranged away from the middle part of the protection body.

[0095] - The side wall can be completely arranged in the gap defined by two segments of the two virtual diagonals without intersecting either of the two virtual diagonals.

[0096] - The thickness (or height) of the housing is less than 50 mm or 60 mm, such thickness or height being typically measured between the bottom wall and the lid of the housing.

[0097] - The housing has a width that can be less than that of the protected body and a length that can be between 200 mm and 1200 mm, for example between 320 mm and 950 mm.

[0098] - The bag is part of a bag unit that includes one or more openings or ports.

[0099] - At least one of the opening ports is formed as a closable duct to allow filling or emptying of the bag.

[0100] - The bag and each closable duct are stored in the internal volume of the housing.

[0101] - In the closed state of the lid, the bag unit is received in the internal volume.

[0102] - The housing has a lower face that faces the outer surface of the storage unit and extends parallel to the reference plane of the protected body in the emptied state of the flexible bag.

[0103] - The housing has a contact surface that contacts the outer surface of the storage unit (when the housing is fastened to the peripheral part and / or to the protected body).

[0104] - The contact surface can extend parallel to the reference plane of the protected body in the emptied state of the flexible bag.

[0105] - The housing fastened along the storage unit has a smaller dimension corresponding to the thickness of the housing measured perpendicular to the reference plane of the protected body, the housing thickness being less than the distance between the bag and the reference plane of the protected body.

[0106] - The support member also supports a duct connected to the port (the duct is typically an integral part of the bag), preferably having a duct that extends between the peripheral part and the bag.

[0107] - The housing is made of a sheet of transparent plastic material.

[0108] - The lid of the housing is a hinged lid.

[0109] - The housing has a hinged lid that is movable relative to an annular frame that defines the opening of the housing for access to the internal volume.

[0110] - The lid extends in a plane parallel to the reference plane of the body.

[0111] - The hinged lid can rotate about a linear hinge.

[0112] - The fastening element includes at least one tab that is formed as an extension from the side wall of the housing, opposite the linear hinge.

[0113] - The bag may comprise two plastic sheets (of liquid-impermeable material) joined together to form the bag.

[0114] - The bag has two sheets welded to each other, each of the two sheets having an inner face for direct contact with the composition contained in the bag.

[0115] - The two sheets may be made of a transparent plastic material suitable for contact with biopharmaceutical compositions.

[0116] - The housing includes side walls defining an internal volume.

[0117] - The housing further includes two opposing tabs, each of the two opposing tabs having a base connected to the side wall, and each of the two opposing tabs being part of a fastening element.

[0118] - The storage unit includes a sliding part supported by a peripheral boundary and formed as an interface with the holding and retaining assembly, the sliding part containing positioning members engaged in and / or clamping the peripheral boundary, and the holding and retaining assembly includes two longitudinal covering parts each extending parallel to the reference plane of the protection body.

[0119] - The interface with the holding and retaining assembly prevents four boundary parts of the protection body from sliding inward (towards its middle part) beyond the stop part or edge (forming at least one abutment surface) of the holding and retaining assembly.

[0120] - Two plates are configured to sandwich the flexible bag for constraining the flexible bag in its filled state, and the protection body is deformable and movable in two gaps respectively defined by the two longitudinal covering parts of the holding and retaining assembly to allow the two plates to move, extend and contract in a transverse direction belonging to the reference plane of the protection body.

[0121] According to a specific feature, at least one of the two plates has ribs projecting outward to locally configure the protection body at least in a peripheral zone around the middle part of the protection body, and all or part of the fastening element is in contact with the outer surface of the storage unit:

[0122] - At a zone included in one of the ribs, and

[0123] - At a distance from the middle part.

[0124] In some variants, the fastening element is entirely provided outside the ribs.

[0125] According to another aspect, a freeze / thaw containment system for containing a biopharmaceutical composition has two plates that respectively form a first surface and a second surface of a protective body, at least one of the first surface and the second surface being an outer surface of a storage unit (the outer surface of the storage unit is formed in an overlapping configuration with respect to a receiving portion of a flexible bag for receiving the biopharmaceutical composition), and one of the outer surface of the storage unit and a mounting kit that covers the peripheral boundary of the protective body has a fastening member disposed above and facing upward with respect to a reference plane of the protective body; and

[0126] wherein at least one of the bag and a housing configured to store the bag has at least one fastening element that cooperates with the fastening member to fasten the bag parallel to the storage unit, and the at least one fastening element is disposed or distributed around a receiving portion of the bag.

[0127] The at least one fastening element may include two or more fastening elements distributed around the receiving portion that defines a second volume (lower than the first volume).

[0128] In some embodiments, the bag has a fastening element and is directly attached to a fastening member on the surface of the storage unit (such that the bag is attached without being stored in a housing). Generally, the bag may have at least two fastening elements that cooperate with the fastening member to fasten the bag to the protective body.

[0129] In some embodiments, two fastening elements are integral with a receiving portion of the bag.

[0130] In some embodiments, two fastening elements are detachably attached to a receiving portion of the bag.

[0131] In some embodiments, two fastening elements are non-detachably attached to a receiving portion of the bag.

[0132] The receiving portion of the bag may be formed of only two sheets of plastic material, typically a transparent plastic material.

[0133] The fastening element extends beyond a circumferential weld that separates the receiving portion of the bag from the peripheral portion.

[0134] At least one pipe for filling and / or emptying the receiving portion belongs to the peripheral portion of the bag.

[0135] The bag has a plurality of fastening elements, and at least one of the plurality of fastening elements maintains the pipe of the bag in a predefined position along the protective bag when fixed to one of the fastening members or when fixed to an auxiliary attachment device of the storage unit.

[0136] According to another aspect, there is provided a method for assembling a freeze / thaw containment system according to the present invention, the freeze / thaw containment system being for storing a biopharmaceutical composition contained in a flexible bag of the freeze / thaw containment system and a protection system for withstanding freezing and thawing of the biopharmaceutical composition. The method includes:

[0137] - selectively sandwiching the flexible bag between two plates of a protection body for covering the flexible bag by a covering portion distributed in the two plates, the flexible bag having a first capacity, the protection body being configured to protect the flexible bag and including two plates, the protection body 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 sides, the two other sides including a first end side and a second end side each perpendicular to the longitudinal axis;

[0138] - using an attachment device for fastening the two plates such that in the assembled state of the two plates, the protection body includes a peripheral boundary extending annularly around the covering portion in a protection body reference plane, the peripheral boundary having at least one opening for receiving at least one port of the flexible bag; and

[0139] - providing a housing defining an internal volume, the bag extending in the internal volume in a filled state, the bag having a second capacity and containing a composition representing the biopharmaceutical composition, the second capacity being lower than the first capacity,

[0140] wherein the housing has at least two fastening elements that cooperate with complementary fastening parts provided on an outer surface of the protection body so as to maintain and fasten the housing to the protection body. Generally, the protection body and the attachment device belong to a storage unit. The assembled state is obtained after configuring the two plates to sandwich the flexible bag and after attaching the housing to the fastening parts, the fastening parts belonging to a rigid peripheral portion surrounding the protection body or to an outer surface of the storage unit formed by the protection body.

[0141] In the assembled state, the two plates respectively form a lower surface and an upper surface of the protection body, at least one of the lower surface and the upper surface being an outer surface of the storage unit, the housing facing the outer surface of the storage unit and having at least two fastening elements that cooperate with the fastening parts so as to maintain and fasten the housing along the storage unit, parallel to the protection body.

[0142] In some embodiments, the fastening zone extends at a distance from a circumferential zone where the attachment device can extend, which helps to have a tight solution.

[0143] The storage unit can be supported by a rigid outer frame that surrounds the circumference of the protective body and / or the circumference of the flexible bag, and the outer frame defines the outer perimeter of the system. The housing can extend completely within the limits of the perimeter of the rigid outer frame. The housing can extend above the protective body and between two elongate profiles belonging to the frame, and optionally the receiving portion of the housing has no contact with this frame.

[0144] In some embodiments, when the housing extends at a distance from the frame or a similar holding and retaining assembly, the housing in the fastened state does not interfere with the displacement and contraction of the boundary portions of the plate during the filling step.

[0145] In some alternatives, when filling the flexible bag with a biopharmaceutical composition in a fluid state, the flexible bag inflates and is movable to reach an adjacent state while corresponding positioning members that are guided in the frame or a similar holding and retaining assembly are configured to constrain the middle of the flexible bag more than the two opposite ends of the flexible bag. In some alternatives, this constraining effect is due to a relatively lower relative displacement between a first positioning member and a first protective body through slot or boss that interacts with the first positioning member compared to the displacement permitted at and / or near the corners of the protective body, and the first protective body through slot or boss is provided at an intermediate position in each of two opposite protective body boundary portions.

[0146] Generally, the void range can be sufficient to allow the corresponding end portions of the protective body to still move inwardly in the filled state of the bag clamped by the plate due to the freezing of the aqueous liquid contained in the bag (i.e., due to the expansion of water upon freezing).

[0147] The contents of the bag stored in the housing and the contents of the flexible bag can be frozen simultaneously, and generally there is no step of displacing / removing the housing from its storage position, in which the housing is attached to the outer surface of the protective body.

[0148] During the following description given by way of non-limiting examples with reference to the accompanying drawings, other features and advantages of the present invention will become apparent to those skilled in the art. Description of the Drawings

[0149] Figure 1 is a perspective view of a storage unit according to a first embodiment of the present invention before assembling two plates of the protective body;

[0150] Figure 2 is a top view showing the assembled Figure 1 storage unit, in which a rib pattern is provided on the top surface of the protective body, and the storage unit includes fastening members for directly or indirectly attaching the bag;

[0151] Figure 3Shows a freezing / thawing containment system, in which, in the emptied state of the flexible bag, the bag is sandwiched between two plates forming a protective body, while the peripheral boundary of the protective body is sandwiched between positioning members;

[0152] Figure 4 Is a perspective view of a freezing / thawing system showing the use of a peripheral frame accommodating an internal positioning member in a filling configuration, in which the positioning member is inactive to limit the inward movement and contraction of the plates sandwiching the flexible bag;

[0153] Figure 5A Is a perspective view of a first exemplary housing for accommodating a bag, the first exemplary housing having fastening elements around the side walls of the housing;

[0154] Figure 5B Is a perspective view of a second exemplary housing for accommodating a bag, the second exemplary housing having fastening elements around the side walls of the housing;

[0155] Figure 6A Is similar to Figure 4 A perspective view, but in which some of the internal positioning members are adjusted to selectively limit the displacement and contraction of the plates in the intermediate region of the protective body, the plates having a ribbed pattern;

[0156] Figure 6B Is Figure 6A A perspective view of the details of the system, showing a portion of a pipe holder engaged on the frame of the system;

[0157] Figure 7A Is a vertical cross-sectional view showing a positioning member suitable for forming a stop, the positioning member being configured to slide inwardly in a contour cavity with a limited stroke while holding a portion of the peripheral boundary of the protective body;

[0158] Figure 7B Is the same vertical cross-sectional view as Figure 7A Showing an adjacent position such that the positioning member stops the inward movement of the corresponding peripheral boundary portion of the protective body;

[0159] Figure 8 Shows details of an exemplary distribution of positioning members provided for holding / maintaining the same longitudinal side of the peripheral boundary of the protective body, thereby allowing limitation of the bulging effect in the intermediate region of the storage unit in the filled state of the flexible bag;

[0160] Figure 9A Is Figure 8 A top view of a liquid-filled flexible bag inside the system, with the protective body and the positioning members not shown;

[0161] Figure 9B Is a view showing Figure 8Side view of the frame-shaped holder inside the system and the flexible bag filled with liquid, with the protection body and the positioning member not shown;

[0162] Figure 10A Is a perspective view of a freeze / thaw containment system capable of supporting and attaching a sample unit, where some of the internal positioning members are adjusted to selectively restrict plate displacement and shrinkage in the middle region of the protection body;

[0163] Figure 10B Shows Figure 10A Top view of a portion of a freeze / thaw containment system having another type of rib pattern, where the sample unit is attached to the system;

[0164] Figure 11 Is a vertical cross-section showing the frame profile, which is suitable for supporting the fixing element and the positioning member integrally formed as a slider that can move inward relative to the fixed frame part. Detailed Description

[0165] In the various figures, the same reference numerals are used to denote the same or similar elements.

[0166] In different figures, the vertical direction, the longitudinal direction, and the lateral direction are based on the freeze / thaw containment system stored horizontally in the rack. The direction perpendicular to the longitudinal direction is the lateral direction. One direction according to the height of the freeze / thaw containment system 1 is the vertical direction, especially reflected by Figure 4 the direction Z in

[0167] In an embodiment of the present invention, the freeze / thaw containment system 1 can be shown, for example, in Figure 4 , 6A and 10A, so as to include a protection body (12, 112, 212) covering two faces of the flexible bag 2 for biopharmaceutical materials (hereinafter referred to as biopharmaceutical composition Q).

[0168] Refer to Figure 1-2 or 3, the protection body 12 or 112 includes two plates 12A, 12B for protecting the flexible bag 2. The two plates 12A and 12B can be made separable. The protection body 12 or 112 includes ribs generally on each of the plates 12A, 12B, while Figure 4 the protection body shown in

[0169] The protection bodies 12, 112, 212 are obtained by clamping two plates 12A, 12B around the circumferential part of the covering part 8 belonging to the protection body 12. For example, by fastening the circumferential parts of the plates 12A and 12B together, the protection bodies 12, 112, 212 are assembled when the empty bag 2 is clamped by the covering part. For this purpose, an attachment device or attachment system 18 is provided to clamp the two plates 12A, 12B. In the assembled state of the two plates 12A, 12B, the protection bodies 12, 112, 212 include a peripheral boundary 80. The peripheral boundary 80 is obtained by fastening the corresponding boundary parts 8a, 8b of the plates. Each plate annular boundary can be constituted by four outer belt areas of the plates 12A and 12B. As Figure 1 and 4 shown, the flexible bag 2 can be directly protected by the two plates 12A, 12B of the protection body 12. The attachment system 18 can be included in the plates and / or included in the positioning member PM, and the positioning member is supported by the protection body 12 at the peripheral boundary 80. In some alternative embodiments, the positioning member PM can form a guiding part for receiving one or more body traversing members. Referring to Figure 6B , a hole 18o can be provided in the positioning member PM for introducing a rod-shaped traversing member that mates with a locking part, a nut or a bolt. Of course, slots can be provided in the protection bodies 12, 112 or 212 to allow the body traversing members to cross the peripheral boundary 80 at multiple positions.

[0170] In other alternative embodiments, particularly as Figure 11 shown, the positioning member PM can simply clamp the peripheral boundary 80, possibly having an interlocking effect due to the bosses Bl2, Bl2' provided in the peripheral boundary 80 (see Figure 1 ). Generally, the positioning member PM (here having a discontinuous distribution) clamps the plate boundary parts, selectively in the peripheral boundary 80, as Figure 3 schematically shown, and once they are introduced into the frame 15 (here in any elongated cavity CP of the frame 15, as Figure 11 shown), generally inside the contours 91, 92, 93, 94, they cannot be disassembled. Therefore, no additional insertion parts IP are required, and the boundary parts 8a, 8b can have bosses or boss parts B12, B12' for engaging with the corresponding reliefs (cavity CF1) of the positioning member PM.

[0171] Referring to Figure 2-3 , the peripheral boundary 80 can extend annularly in the reference plane P of the protection body, and the peripheral boundary 80 has at least one opening 80a capable of receiving at least one port 24 of the flexible bag 2. Two front ports 24 can be provided. For example, one port forms an inlet of the flexible bag 2, and the other port forms an outlet of the flexible bag 2.

[0172] In the unfilled state of the bag 2, the protection bodies 12, 112, 212 can extend in a plane along the protection body reference plane P.

[0173] System 1 is adapted to accommodate, freeze / thaw a biopharmaceutical composition Q (see Figure 7B ). Refer to Figure 4 , 6A and 10A. Such a system 1 is horizontal here and uses a horizontal frame. However, in a variant, this system can also be vertical, such that the bag 2 can be stored vertically in the cavity of a vertically framed holder (for example, see the bag vertically received by using a rigid grooved frame as described in WO 03037082). It can be meaningful to use a rectangular frame 15 with inwardly open slots or cavities CP in order to form a tight holder capable of accommodating the corresponding boundary portions of the storage unit 10.

[0174] The flexible bag 2 is typically a 2D-type bag, which is bounded by two longitudinal sides LS1, LS2 and has a substantially rectangular shape on its two main outer surfaces without predefined folds, as Figure 1 shown (empty bag). Thus, the bag 2 extends substantially in a plane in the unfilled state. The bag 2 can have two main walls W1, W2. These walls W1, W2 can be directly welded to each other at the welds or peripheral seals J to define an internal volume for accommodating the biopharmaceutical fluid Q. More generally, the flexible bag 2 can be made of any suitable material for accommodating the biopharmaceutical composition Q and form a freezer bag with a large capacity that can typically be higher than or equal to 5L. More generally, the flexible bag 2 has a first capacity, and the bag 2 can expand at least in the intermediate region away from the four bag corners to increase the thickness, and such thickness increases with the filling level of the bag 2.

[0175] Refer to Figure 1 , the flexible bag 2 extends in the main plane XY, which is a horizontal plane here. The bag 2 has a longitudinal axis A parallel to its long side, which in the non-limiting illustrated embodiment is the two longitudinal sides LS1, LS2 here. The flexible bag 2 is sandwiched between plates 12A, 12B and cannot be removed without first removing at least one of the two plates 12A, 12B. The plates 12A, 12B are firmly attached to each other and are generally not fixed to the bag 2. In addition to the attachment system 18, a holding and retaining assembly HR can also be provided for holding the unit composed of the protection body 12 and the attachment system 18.

[0176] The storage unit 10 provides effective protection during freezing, storage, and thawing operations, while the biopharmaceutical composition Q is accommodated in the receiving portion 2r of the flexible bag 2. Due to the difference in materials (more rigid for the two parts forming the plates 12A, 12B), the covering portion 8 of the protection body 12 is not as flexible as the receiving portion 2r of the flexible bag 2. When placed horizontally and maintained by the holding and retaining assembly HR, the two plates 12A, 12B respectively form the lower surface and the upper surface of the protection bodies 12, 112, 212.

[0177] Reference Figure 2 , at least one of the lower surface and the upper surface is the outer surface of the storage unit, optionally provided with fastening members 146', 147', 148' for allowing direct or indirect fastening of the bag 2'.

[0178] Reference Figure 6A , the storage unit 10 can support the bag 2', where it is independent of the holding and retaining assembly HR. This bag 2' can accommodate the composition representing the biopharmaceutical composition Q. The capacity of the bag 2' is lower than the first capacity and preferably has a second capacity of a lower order of magnitude (i.e., at least 10 times lower).

[0179] In another alternative as shown in Figure 10B , the bag 2' is inside the housing 130 and is supported by the frame 15 or any suitable holding and retaining assembly HR such that the bag 2' extends above the protection body 12, generally parallel to the protection body 12.

[0180] The bag 2' and / or the housing 130 storing the bag 2' can be provided with fastening elements 132, 133, 134, which cooperate with the fastening members 146, 147, 148 or 146', 147', 148' to fasten the bag 2' (directly or indirectly) to the protection bodies 12, 112, 212 and / or to fasten to the mounting kit provided in the frame 15. In order to attach the housing 130 to extend along one of the outer surfaces S, S' of the storage unit 10, the fastening elements 132, 133, 134 can be distributed around the receiving portion 200 of the bag 2', here around the housing 130 that can include a compartment for accommodating the receiving portion 200. The receiving portion 200 of the bag 2' is the portion of the bag 2' that defines the second capacity.

[0181] Here, Figure 5A and 5B show two variations of the housing 130 with different arrangements of the fastening elements 132, 133, 134.

[0182] In Figure 5A 's alternative, in as Figure 10BIn the assembled state shown in particular, the fastening elements 132, 133, 134 extend substantially in the same direction as, or transverse to, the length extension of the protection body 12.

[0183] Each bag 2 can be filled with a solution or fluid composition Q to be frozen and is kept slightly compressed between two plates 12A, 12B that act as heat exchange surfaces. For this purpose, the plates 12A, 12B completely cover the bag 2 at least in the fluid receiving portion 2r, i.e., the region that defines the internal volume of the bag 2 (i.e., generally all the walls W1, W2, possibly excluding the annular seal J and any optional outer extensions). In the illustrated embodiment, the bag 2 is completely covered by the protection bodies 12, 112, 212 formed by the two plates 12A, 12B. During the freezing / thawing operation, the plates 12A, 12B are cooled / heated by circulating a heat transfer fluid, for example, from an external programmable refrigeration unit. The slight compression (accommodation effect) provides improved contact and heat transfer, resulting in a frozen bag having a generally pillow shape (see in particular Figure 4 and 6A ).

[0184] The bag 2 sandwiched between the plates 12A, 12B can be placed in a frame 15, here a rigid frame compatible with temperatures below 0 °C, so as not to damage the internal material during handling and transportation. Referring to Figure 4 and 6A , the frame 15 can be part of a support structure. Here, the frame 15 is a modular part of a device or bracket that can be located in a freezing apparatus. Rollers (not shown) can be provided to facilitate transportation. The frame 15 is generally a rectangular protection frame that exposes the outer surfaces S, S' of the protection body 12 but forms four protection sides around the storage unit 10. The frame 15 can be included in a holding and retaining assembly HR that also includes positioning members PM engaged in the peripheral boundary 80 of the protection bodies 12, 112, or 212, as particularly shown in Figure 8 . The assembly can include a plurality of feet that may be tubular in shape and suitable for stacking.

[0185] More generally, the bag 2, the protection body 12, the sample unit SU (including the bag 2' and the housing 130), and the holding and retaining assembly HR can define a freeze / thaw containment system 1, where 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 bag 2 is placed inside the storage unit 10 and covered by the two plates 12A, 12B. The protection body 12 has a peripheral boundary 80 engaged in the gap of the holding and retaining assembly HR. The storage unit 10 is adapted for freezing, storing, and thawing a biopharmaceutical fluid / composition Q contained in the flexible bag 2, and the fluid is typically introduced after the storage unit 10 is assembled with the flexible bag 2, which is usually a disposable bag contained in the protection body 12, and after the storage unit 10 is installed in the frame 15.

[0186] In Figure 6A and 7B it can be seen that the bag 2 is contained in the storage unit 10, inside a protection body held by a frame profile or similar protection part. This storage unit 10 includes a protection body 12 and positioning members PM that form an interface for mounting the storage unit 10 in a protective housing or assembly HR that includes two or four protection parts, which can be elongate profiles 91, 92, 93, 94. Using four rigid profiles helps to form a rectangular frame 15. Optionally, the bag 2 can have a type (possibly having a capacity of 50L or more), and thus is a sterile, disposable, discardable container that is adapted to be enclosed by the frame 15 obtained after assembling the profiles 91, 92, 93, 94 or similar holding elements.

[0187] In some alternatives, the holding and retaining assembly HR can have fewer than four components so as not to form a rectangular frame. For example, only three components may be sufficient, where a transverse component interconnects two longitudinal covering parts 31, 32 that are parallel to the longitudinal axis A of the bag 2. Figure 3 Only two covering parts 31, 32 that can be integral with the feet or associated with the transverse structural members are shown. In some alternatives, the covering parts 31, 32 can extend vertically. In the illustrated embodiment, the covering parts 31, 32 extend horizontally, which can be preferred when the bag contains more than 50L, such as about 75L or at least 100L. Figure 4 、 10AFigures 10 and 11 show exemplary parallel covering portions 31, 32 including two single-piece profiles 93, 94. Each single-piece profile 93, 94 may be hollow, each defining an elongate cavity CP for insertion of a positioning member that allows positioning of the storage unit 10 and a reference plane P, generally perpendicular to the legs 115 connected to the covering portions 31, 32. The legs 115 allow the reference plane P to be offset upward relative to the ground level. This helps to allow vertical expansion of the covering portion 8 belonging to the protection body 12, which extends substantially horizontally here.

[0188] Reference Figure 3 and 7A -7B, the bag 2 may have an initially planar form or shape in the emptied state. The bag 2 is flexible so as to be inflatable and may be made of a pair of flexible sheets (which form respective walls W1, W2), having a rectangular or other planar form, and joined together at four peripheral edges to provide an accommodation volume (an internal volume for the composition Q) between the sheets 21, 22, the sheets being spaced apart at a distance in the filled state. One or more openings or ports 24 may be provided, for example formed as closable ducts between opposite portions of the peripheral edges of the sheets, to allow filling or emptying of the bag 2.

[0189] The bag 2 is also designed to provide a high surface area / volume ratio at a thin thickness or spacing. By way of non-limiting example, the bag 2 may have rectangular dimensions of about 600 mm × about 1300 mm or 1400 mm, and / or a holding volume between about 10 liters and about 120 liters or 200 liters (preferably between 50 liters and 120 liters), and / or a spacing or bag thickness (height along the Z direction) between about 8 mm or 10 mm and about 25 mm or 30 mm.

[0190] Each bag 2 may be made of any suitable biocompatible material and preferably promotes heat transfer between the interior and exterior of the bag 2. To reduce or avoid damage to the bag 2 due to expansion of the biopharmaceutical material during cryopreservation, it is preferred that the material will have a glass transition temperature lower than that of the biopharmaceutical material. By way of non-limiting example, each bag 2 may be made of a multilayer composite material made only of thermoplastic materials such as including polyethylene (at least a PE layer).

[0191] The protection body 12 and the flexible bag 2 include a longitudinal direction X and a transverse direction Y. The protection body 12 and the flexible bag 2 each include a longitudinal side and a transverse side. The longitudinal axis X1 of the protection body 12 may be placed in an intermediate vertical plane that separates the two symmetric halves of each plate 12A, 12B of the protection body.

[0192] The bag 2 optionally includes one or more conduits T joined to the front end (at the lateral sides), the conduits extending transversely with respect to the longitudinal sides LS1, LS2. More generally, the bag 2 can include a hose / conduit or any suitable number of conduits connected to the periphery of the useful part of the bag 2. This useful part is here formed by two main walls W1, W2.

[0193] Protected subject

[0194] Reference Figure 1 and 3 -4, the protection body 12 or 112 includes or has two plates 12A, 12B for protecting the flexible bag 2. The plates 12A, 12B are completely separated and here do not have hinge or connection parts. Generally, the plates 12A, 12B are two separable parts. These parts are relatively rigid, for example rigid enough such that they cannot form a fold line with a bending angle greater than 45°. Thus, the plates 12A, 12B are configured to remain relatively flat. The protection bodies 12, 112, 212 include a longitudinal axis X1 and have four sides 120a, 120b, 120c, 120d, the four sides including two longitudinal sides 120c, 120d extending parallel to the longitudinal axis X1 and two other sides, the two other sides including a first end side 120a and a second end side 120b each perpendicular to the longitudinal axis X1.

[0195] Reference Figure 1-3 of the embodiment, in each of the plates 12A, 12B, a first set of ribs includes ribs R1, R2, R2', 800 arranged near the peripheral boundary 80. An optional second set of ribs can include ribs R3, R4, 83, 84, 85, 86 arranged at a greater distance from the peripheral boundary 80. Such ribs in the second set can surround one or two panel portions PP, PP1, PP2 in each outer surface S, S' of the protection bodies 12, 112, the panel portions generally forming rectangular panels.

[0196] In some variants, the number of ribs can be reduced or the ribs can be removed. When providing elongate ribs, the elongate ribs are preferably wide enough to form grooves G1, G2 having an arcuate profile (as seen in cross-section). Each elongate groove can have an internal width of at least equal to 10 mm, typically higher than or equal to 15 mm or 20 mm. Due to such grooves, a wavy profile can be obtained locally.

[0197] In the illustrated embodiment, the protection bodies 12, 112, 212 preferably have an attachment device / system 18 for fastening the two plates 12A, 12B such that in the assembled state of the two plates, the protection bodies 12, 112 include a peripheral boundary 80 extending annularly in the protection body reference plane P, asFigure 3 and 4 as shown in 4 . In some alternatives, the peripheral boundary 80 extending in the internal gap delimited by the frame 15 is generally a rib-free boundary. In a variant, one or more ribs R1 adjacent to the boundary portions for the mutual attachment of the plates 12A, 12B may extend in such a gap.

[0198] The protection body may comprise:

[0199] - A first end side 120a, which is formed by the ends E1 of the two plates 12A, 12B in the assembled state of the protection bodies 12, 112, 212, and

[0200] - A second end side 120b, which is formed by the ends E2 of the two plates in the assembled state of the protection body 12, 112.

[0201] One or more ports 24 may project axially outward from the second end side 120b. Here, the part of the front edge of the bag is thus accessible.

[0202] In the emptied state of the bag 2, the two plates 12A, 12B respectively form the first surface S' and the second surface S of the protection bodies 12, 112 covering the bag 2. When having a substantially horizontal configuration, the first surface is the lower surface, and the second surface is the upper surface. Clamping members 146', 147', 148' may be provided on one of these surfaces S, S', near the end side selected among the first end side 120a and the second end side 120b. Figure 2 and 6A The embodiment of 6A shows a way with small individual zones, which may be formed as convex parts or embossments for fixing the sample unit SU at the corresponding concave part, cavity or orifice 136. Although the clamping members 146', 147', 148' are all provided here on the same part of one of the two plates forming the protection body 12, at least one of the clamping members may also be included in the holding and retaining assembly HR, that is, in the zone extending around the bag 2 and the covering part 8. For example, the sample unit SU may have several arms or tabs extending from the housing 130 accommodating the bag 2', and at least one of the arms or tabs is a clamping element 132 attached to the lateral profile 91 or a similar rigid part included in the frame 15 of the assembly HR.

[0203] In Figure 4 and 10AIn the embodiment of -10B, the sample unit SU is not supported by any part of the protection bodies 12, 112. In contrast, the arms or tabs of the sample unit SU extend from the housing 130 for engaging the mounting kit including the frame 15, where each of the arms or tabs forms a respective fastening element 132, 133, 134 that generally engages such a mounting kit at a knot located above and around the protection bodies 12, 112. At least one of the lower surface S' and the upper surface S may be a surface having a plurality of ribs distributed in two opposite portions of the surface, and the two opposite portions are longitudinally opposite portions. Preferably, this plurality of ribs includes a first transverse rib portion 4 near the first end side 120a and a second transverse rib portion 6 near the second end side 120b.

[0204] Due to the width of the corresponding grooves G1, G2 formed by the ribs and / or the height of the ribs (the depth of the grooves G1, G2), such transverse ribs provide a folding effect. This promotes the local expansion of the plates 12A, 12B, regardless of the planar structure of the peripheral boundary 80 forming the protection reference plane P. Generally, in the corner region CR, the height of the first transverse rib portion 4 and the second transverse rib portion 6 decreases as the space from the corner vertex of the plate having such rib portions 4, 6 decreases.

[0205] Thus, when the height of the corner rib portion extending in the corner region CR decreases, excessive expansion that may cause unwanted folding (along the diagonal) can be restricted or prevented. In other words, in the four corner regions CR of each of the plates 12A, 12B, the folding effect can actually be reduced. More generally, when the flexible bag 2 sandwiching the filling is between the plates 12A and 12B, it is helpful to construct the plates 12A, 12B using the first transverse rib portion 4 and the second transverse rib portion 6 in order to promote the diffusion of the fluid towards the boundary 80 and towards the corners of the protection bodies 12, 112.

[0206] This is meaningful in order to have or improve the bulge holding effect. In fact, the more the fluid can be distributed towards the four corners, the smaller the bulge of the bag 2 in the middle region. The protection bodies 12, 112 are generally capable of moving in the gap of the holding and retaining assembly HR, as described in more detail below. In addition, when the thickness / dilation difference between the middle region including the center C of the protection body and the edge of the covering portion is too obvious, the structural effect of the ribs can prevent the folding lines from forming substantially along the diagonals DL1, DL2. In some alternatives, there are no corner ribs.

[0207] Some detailed embodiments of the protection body 12 or 112 with a ribbed pattern will be described below.

[0208] As Figure 1 、 2, the plates 12A, 12B shown in 4 and 7 correspond to a first embodiment of the protective body 12 in which a plurality of ribs are provided. In each outer surface of the plate, ribs are provided such that the inner surface has grooves. Some of the grooves G1, G2, for example Figure 1 as shown in, include transverse groove portions extending perpendicular to the longitudinal axis X1 and near the opposite end sides 120a, 120b of the protective body. An annular rib R1 protruding upward in the outer surface S or S' may be provided to define a groove G1 having an annular shape on the inner surface of the plate. Two separate ribs R2, R2' protruding upward in the outer surface S or S' may be provided to define one or two grooves G2 each having an annular shape on the inner surface of the plate.

[0209] Thanks to the ribs R1 and R2, R2', a pair of transverse rib portions 4, 6 parallel to the Y-axis direction (perpendicular to the longitudinal axis X1) here can be arranged near the corresponding end sides 120a, 120b. In other words, these ribs form a first transverse rib portion 4 near the first end side 120a and a second transverse rib portion 6 near the second end side 120b.

[0210] Referring to Figure 1-2 , it can be seen that each of the plates 12A, 12B can be rectangular, having four corner regions CR, and two virtual diagonals DL1, DL2 (diagonals of the plate) each intersecting a pair of corner vertices of the four plate corners. More precisely, each of the two virtual diagonals DL1, DL2 intersects:

[0211] - A first series of corner ribs C1, C2, which are near the first end side 120a and protrude outward in a direction perpendicular to the reference plane P of the protective body, and

[0212] - A second series of corner ribs C1, C2', which are near the second end side 120b and protrude outward in a direction perpendicular to the reference plane P of the protective body.

[0213] Each of the corner ribs C1, C2, C1', C2' is bent and connects two rib portions perpendicular to each other. Here, the annular rib R1 can thus respectively include two pairs of corner ribs C1, C1'.

[0214] Although Figure 1-2 's embodiment shows a rib pattern in which the ribs can be regarded as peripheral ribs arranged around the central panel portion PP of the plates 12A, 12B, but Figure 3 and 6A show that the ribs can be provided in the intermediate region MR and may extend transversely to two separate panel portions PP1, PP2 of the same plate.

[0215] Although in Figure 1-3In the embodiments of FIGS. 6A, the same rib pattern is provided in the two complementary plates 12A, 12B, but some differences may be provided in variants. Optionally, one or both of the plates may lack ribs.

[0216] Plates 12A, 12B each form a hardening layer when overlapping and preferably completely covering the main walls W1, W2. The thickness of each plate 12A, 12B before thermoforming is about 1.27 mm and / or may be less than 2 mm, provided that the plastic material of the plate has a density higher than 1.10 g / cm 3 , preferably higher than 1.15 g / cm 3 (usually not higher than 1.5 g / cm 3 or 1.6 g / cm 3 ). The plate material may have a tensile strength at break generally in the range between 45 MPa and 75 MPa, such as between 50 - 60 MPa, usually 52 - 59 MPA (standard test ASTM D638).

[0217] Although the illustrated embodiment shows the protection body 12 completely covering both main walls W1, W2 through the covering part 8, other dimensions may be used for the covering part 8. For example, the protection body 12 may only cover the transverse strip portions of each wall W1, W2 at a certain distance from one of the opposite edges of the two bags. In addition, one or more complementary protection bodies may be used to cover at least one of the end portions of the walls W1, W2.

[0218] Details of an embodiment of an attachment system for attaching boards together

[0219] The protection body 12 may have a covering part 8 for covering the bag 2 and two opposite boundary parts 8a, 8b at the two longitudinal sides 120c, 120d of the protection body 12. In the unfilled state of the bag 2, the protection body 12 extends flat along the protection body plane P and remains flat. Thanks to the attachment system 18, the plates 12A, 12B remain attached at several positions of the peripheral boundary 80 during the processing of the system 1.

[0220] The protection body 12 may be transparent, for example, the bag 2 is also transparent. The plates 12A, 12B may have a general curvature but cannot be easily folded (the flexibility is basically as low as that of PET). The peripheral boundary 80 may form an annular attachment area where folding is not permitted.

[0221] Reference Figure 2 , the protection body 12 also has an attachment system 18 for fixing the two plates 12A, 12B to each other around the covering part 8. The plates 12A, 12B can be detachably fixed to each other by the attachment system 18 distributed in the peripheral boundary 80.

[0222] Optionally, the attachment system 18 may include a plurality of snap fasteners. One of the two plates 12A, 12B includes a first element of a snap fastener, and the other plate includes a second complementary element of a snap fastener. Referring to Figure 2 , the second element 18b (possibly a convex element) engages the first element 18a (possibly a concave element) in a direction parallel to the vertical axis Z.

[0223] Alternatively, the attachment system 18 is a non-detachable system, which means that once the two plates 12A, 12B are fixed to each other, it is no longer possible to disassemble the two plates 12A, 12B from each other.

[0224] In Figure 1-2 a non-limiting embodiment of, the protection body 12 may include:

[0225] - snap fasteners 18a, 18b, which are on the lateral sides 120a, 120b and on the two boundary portions 8a, 8b;

[0226] - and / or apertures 102 (see Figure 6B and 7A ), which are for receiving an insertion part IP or a similar anchoring member not included in the plates 12A, 12B.

[0227] In an alternative where snap fasteners or similar fastening portions included in the plates 12A, 12B are used, such fastening portions may be symmetrically arranged on the lateral ends of the two plates 12A, 12B. Alternatively, the protection body 12 may include more snap fasteners on the front side 120a than on the rear side 120b.

[0228] In some embodiments, the fastening portions for the mutual attachment of the plates 12A, 12B may also form protruding reliefs or cavities for receiving / inserting the positioning member PM. For example, Figure 1 at least two of the embossments Bl2, Bl2' shown in Figure 11 may cooperate with an elongate positioning member PM (formed here as a parallelepiped part) shown in Figure 3 or 8 (non-limiting examples) by forming a receiving portion. The insertion effect is obtained by pushing the insertion face of each positioning member PM towards a complementary receiving portion provided in the peripheral boundary 80. Each plate 12A, 12B may receive such positioning members PM, which typically have a regular distribution around the covering portion 8 of the protection body 12, as shown, for example, in

[0229] More generally, the attachment system 18 can typically include any suitable mechanical fasteners disposed between the covering portion 8 and the longitudinal sides 121, 122. Generally, two opposite boundary portions 8a, 8b can be regarded as parts of a fastening assembly that is provided to prevent any positional offset between the two plates 12A, 12B once they are fastened to each other at least at the two boundary portions 8a, 8b.

[0230] As Figure 2-4 visible in FIGS. 6A - 6B and 7A - 7B, when the two plates 12A, 12B are fixed to each other, they sandwich the flexible bag 2. The planar plate 12A forming the lower surface S' of the protective body 12 presses against the lower surface of the flexible bag 2 relative to the vertical axis Z. Similarly, the planar plate 12B forming the upper surface S of the protective body 12 presses against the upper surface of the flexible bag 2 relative to the vertical axis Z. The two plates 12A, 12B can have planar dimensions that are substantially the same as the planar dimensions of the flexible bag 2.

[0231] Retention and holding assembly

[0232] Referring Figure 2 to 3 FIGS. 3, 4 and 10A, the holding and retaining assembly HR includes a frame 15 and a positioning member PM that optionally cooperates with or is part of the attachment system 18. Here, the positioning member PM covering or included in the attachment system 18 can move relative to the frame 15, which acts as the fixed part of the holding and retaining assembly HR. In some embodiments, the two longitudinal covering portions 31, 32 include profiles and can be regarded as belonging to the holding and retaining assembly HR. The positioning member PM can be introduced into the profile of the frame 15 or can be attached to similar covering portions 31, 32 before assembling the assembly HR (usually before assembling the frame 15).

[0233] For example Figure 3 the two covering portions shown in FIG. 10 are arranged to maintain the two longitudinal boundary portions 8a, 8b of the peripheral boundary 80 while allowing the two plates 12A, 12B to move, extend and contract in the transverse direction belonging to the reference plane P of the protective body. As Figure 4 shown in 11 FIGS. 11 and 12, the two longitudinal covering portions 31, 32 can include two profiles 93, 94 that respectively define internal cavities CP. In a non - limiting embodiment, the gap can be the corresponding internal cavity CP of such covering portions. Each of the two longitudinal covering portions 31, 32 can include a profile that is substantially C - shaped or U - shaped to define one of the internal cavities CP.

[0234] Referring Figure 2 to 6AWith respect to FIGS. 10B - 11, it should be understood that the bag 2 is sandwiched between the plates 12A, 12B without interfering with the hoses or pipes T each having an end connector 17. The protection bodies 12, 112, 212 can be assembled first, and then the two protection parts 31, 32 can be assembled to complete or cover the attachment device 18.

[0235] Generally, the holding and retaining assembly HR includes a frame 15 having four sides, which has a rectangular shape here. The longitudinal covering parts 31, 32 can be protected within the profiles 93, 94 forming the two longitudinal sides of the frame 15. Other covering parts provided along the transverse sides of the protection bodies 12, 112, 212 can also be included in the attachment system 18. Optionally, such other covering parts can be accommodated / protected within the profiles 91, 92 forming the two transverse sides of the frame 15.

[0236] 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 manner form the four sides. Two of the four profiles are included in or form the two longitudinal covering parts 31, 32. These two profiles 93, 94 are formed as two longitudinal sliding members for respectively receiving at least three of the positioning members PM, which are separate and distributed along the length of the frame 15. Optionally, the two other profiles 91, 92 can also form sliding members, here transverse sliding members, to accommodate the transverse sides 120a, 120b of the protection bodies 12, 112, 212. Similar positioning members PM can be slidably mounted in the track - like profiles 91, 92.

[0237] The holding and retaining assembly HR can horizontally or vertically maintain the protection body, and the frame 15 also helps to form a peripheral protection around the protection bodies 12, 112, 212. The peripheral frame 15 accommodates the internal positioning members PM, which have a dimension (along the same direction) greater than the corresponding dimension of the opening at the open sides of the profiles 91, 92, 93, 94 along the Z - direction. Although four similarly constructed profiles 91, 92, 93, 94 are provided here to accommodate the positioning members PM on each of the four sides, variants with one or two sides without such positioning members PM can be provided. In addition, variants with another type of covering parts 31, 32 can be provided, which are capable of performing shrinkage management for some sides of the protection bodies 12, 112, 212, or where such shrinkage management is not possible (e.g., if the capacity of the bag 2 is relatively low).

[0238] Figure 4 The structure shown in FIG. 13 is helpful for a bag 2 of relatively large capacity, which may have a significant bulge B without any shrinkage management at the peripheral boundary 80.

[0239] The holding and retaining assembly HR can be assembled after the positioning member PM is installed in the peripheral boundary 80. As Figure 10A-10B shown, the corner sections 15c can be used between adjacent vertical profiles. Before or after placing the longer profiles 93, 94, at least two corner sections 15c can be snapped onto the lateral profile 91 (here the rear profile). The positioning member PM can be arranged outside the corner sections 15c. One or two corner sections 15c of the frame 15 and at least three profiles 91, 93, 94 can be provided to form a mounting kit for supporting the protection body 2. The mounting kit further serves as a receiving device for attaching the sample unit SU.

[0240] Reference Figure 10A-10B , the clamping members 146, 147, 148 can be distributed:

[0241] - on two corner sections 15c; and

[0242] - on two support attachments directly joined in the longitudinal profiles 93, 94 or similar covering parts of the holding and retaining assembly HR.

[0243] Here, three separate support members belonging to the holding and retaining assembly HR can form a rigid peripheral part that combines the first function of attaching / holding the storage unit 10 along a generally horizontal plane and the second function of forming several clamping members 146, 147, 148, each of which extends above the protection body 12 to interlock with complementary clamping elements 132, 133, 134 extending around the housing 130 of the sample unit SU or a similar receiving part.

[0244] The rigid peripheral part can be the frame 15 as shown in Figure 6A or 10A. When four corner sections 15c interconnect the frame profiles 91, 92, 93, 94, the peripheral boundary 80 can have only one open side located between two corner sections, laterally covered by the profile 92 with an opening. At the frame side opposite such a profile opening for the port 24, two corner sections 15c can directly define two clamping members 146, as shown in Figure 10A-10B for clamping the housing.

[0245] Of course, any suitable rigid covering part that can protect the areas / locations of the storage unit 10 and the sample unit SU can be used to form the frame 15 in various ways. Preferably, the frame 15 can surround the housing 130 of the sample unit SU and maintain the sample unit SU in a position close to the plate of the protection body, with or without contacting the protection bodies 12, 112, 212.

[0246] Pipe retainer

[0247] Reference Figure 6A , two hoses or tubes T are typically connected to the front edge of the flexible bag 2. At the longitudinal end opposite the front longitudinal edge, the rear edge of the flexible bag 2 may extend substantially parallel to the front edge. Although each tube T may be flexible and have a length longer than the lengths of the longitudinal sides LS1, LS2 of the bag 2, hoses / tubes of any size may be used. Each tube T may be maintained substantially parallel to the protection body reference plane P by being attached to a tube holder disposed in or attached to the frame 15 of the assembly HR.

[0248] Each hose / tube T is provided with a connector 17 for fluid connection (typically a connection to another biopharmaceutical device). Thus, the connector 17 makes it possible to fluidly connect the flexible bag 2 to another element, such as a tank. In the storage position of the tubes by using the fixing members MF1, MF2, each connector 17 may be located between the longitudinal rear side 120b and the intermediate region MR of the protection body 12.

[0249] Reference Figure 4 , one or more in the elongation profile, here the profile 94, may be provided with one or more fixing members MF1, MF2 for supporting at least one tube T connected to the port 24 or included as an extension of the defined port 24 in the bag 2. The tube holders including the fixing members MF1, MF2 may be distributed at least two spaced-apart positions along the side portions of the frame 15 in the peripheral region of the system 1.

[0250] The frame 15 may be provided with clamping members and / or grooves G9 (see Figure 11 ) for holding one or two hoses / tubes T connected to the bag 2 via the port 24 (see Figure 10B ), thus forming a tube holder. Such a tube holder has holding portions distributed on 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 contain portions of such holding members for holding the hose T above the protection body 12 in a preferred alternative. Depending on the ease of access to the top or bottom of the protection body, in some variants, the tube holder may also extend below the protection body 12 by using a groove G9 arranged below the protection reference plane P.

[0251] It should be understood that the pipe holder is completely arranged outside the cavity CP so as not to interfere with the peripheral boundary 80 and thus does not interfere with the degrees of freedom of movement of some of the positioning members PM. When the groove G9 is provided in the longer profiles 92, 94, the groove G9 can be substantially as long as the flexible bag 2 and / or as long as the space defined between the opposite lateral profiles 91, 92. This allows flexibility in using the groove G9 to position the fixing member MF1 with the anchoring part.

[0252] In a first alternative, the fixing member MF1 of the pipe holder comprises one or more anchoring parts having an anchoring relief 160, as Figure 11 is evident, having a shape complementary to the receiving groove G9 in one of the longer profiles 93, 94. Each anchoring part may also have an abutting end 162 that contacts the surface of the inner section 15a (here a substantially vertical surface). The anchoring part may extend upward from the joint part that joins the anchoring relief 160 and the abutting end 162, and such a joint part is optionally a hollow part or a recessed part to improve the deformation of the anchoring relief that can be clamped in the groove G9. Here, the anchoring part is inclined (inwardly) with respect to the Z direction. The sample unit SU does not overlap with the frames 93, 94, which can be suitable for easily positioning the feet 115 or similar vertical struts, thus allowing two systems 1 to be stacked without interfering with the attachment / detachment operation of the sample unit SU.

[0253] In a variant, the anchoring part can be fitted or screwed into a concave part included in the profile 93 or 94, or has a concave part end that mates with the convex part of the profile 93 or 94. This is preferably a detachable attachment.

[0254] Generally, the anchoring part can further include a fastening member 147 at its upper end for keeping the sample unit SU parallel to the frame 15 and thus substantially parallel to the reference plane P in the illustrated embodiment. The one-piece construction of such a fixing member MF1 simplifies the installation steps. It can also help to accommodate more than one component, especially when there is also a sample unit SU supported by the fixing member MF1, and the positioning of which can be easily adjusted along the length of the profile 93 or 94. Other suitable fixing members can be used for the detachable attachment of the anchoring part to the frame 15, and such anchoring parts act as fastening members to the frame 15.

[0255] In some alternatives, the anchoring part or a similar holding part is not used for attaching the pipe T and can only act as a fastening member 147 or 148.

[0256] It can be seen that the sample unit SU is attached above two longer profiles 93, 94 at a certain distance from the rear corner section 15c and is also attached to one or more fastening members 146 arranged at the rear end of the frame 15. In some alternative embodiments, such additional fastening members may be formed near the rear end of the protection body, typically outside the outer perimeter 80.

[0257] Referring Figure 4 to the alternative embodiments shown in FIGS. C and 6E, the hose / tube T can simultaneously receive and / or guide in:

[0258] - the groove G9 (in the part of the groove G9 that is away from the rear profile 91 and close to the front profile 92), and

[0259] - the blocking groove BG of the anchoring part.

[0260] This contributes to a compact arrangement of the entire system 1, where the outer circumference of the system is only defined by the profiles, here by the outer section 15b of the frame 15, effectively acting as protection for the bag 2 that has been sandwiched between the two plates 12A, 12B.

[0261] The fixing member MF1 can be easily disassembled because a simple rotation of the anchoring part may be sufficient to release this part from the groove G9. No tool is required to remove the hose / tube T from the guiding groove G9 because the end of the tube is already available / thus outside the groove G9 by being clamped in the blocking groove BG that is very short compared to the elongate groove G9.

[0262] Referring Figure 6A-6B to FIGS. 6 and 7, the fixing members MF1, MF2 can include at least one fixing element 110, which can be snapped onto the frame 15 here by engaging with the outer part of the rail-shaped profile of the frame 15. For example, the fixing element 110 is a bracket that partially surrounds the receiving profile, and the receiving profile can be one of the longitudinal profiles 93, 94 or another profile 91, 92. Here, the fixing element 110 is a single part made of plastic material and has an inner face F110 that can locally match the outer face F94 of the corresponding profile 94. The fixing element 110 can be engaged at a position opposite to the open side of the profile.

[0263] The fixing element 110 is C-shaped or U-shaped in cross-sectional view here, thus forming a bracket with an almost closed inner face F110. The bracket defines an inner space or notch for receiving a part of the profile 94. Two opposite edges 110b project towards each other from opposite parallel parts of the inner face F110 so as to narrow the open side of the bracket, as Figure 6BAs shown. Two opposite edges 110b are holding edges that contact the inner side of the receiving profile, such that outward movement of the fixing element 110 relative to the receiving profile (here the profile 94) is prevented.

[0264] The protruding pin 110a can be provided in this part (or vice versa in the receiving profile) so as to form an inwardly protruding indexing member. The fixing element 110 further includes a clamping portion 113 that forms a receiving cavity defined by the recessed inner surface 113a. A portion of the outer wall of a pipe, which can be cylindrical, can be inserted and fitted into this receiving cavity. When the protection body and the bag 2 extend horizontally, the portion of the pipe T received in one or both cavities of the fixing element 110 can extend completely above the plane XY.

[0265] Compared with the notch for receiving the profile portion, the cavity defined by the surface 113a can be offset inwardly. The farther the flexible pipe T is from the periphery of the system 1, the lower the risk of accidentally handling and disconnecting this hose or pipe T, for example during the transportation step. However, this pipe T remains easily accessible to the operator here.

[0266] Reference Figure 6B , the pin 110a can extend parallel to the Z direction and project from the inner face 110. This pin 110a or a similar indexing member, as well as the clamping portion 113 or a similar portion for holding the pipe T, can be provided on the same C-shaped or U-shaped branch of the element 110. More generally, the indexing element is provided on the inner face F110, while the portion 113 for holding the pipe T extends relatively from the outer face of the fixing element 110.

[0267] The pin 110a is received in a notch or orifice of the receiving profile, such notches or orifices opening outwardly. A pair of two opposite notches 94a, 94b can be provided at the same longitudinal position (position considered along the X direction) of the profile 94, such that the notch 94a or 94b is always available regardless of the relative position of the pipe T with respect to the frame 15.

[0268] When engaged in the notch 94a or 94b, the pin 110a prevents sliding (longitudinal sliding) of the fixing element 110 relative to the receiving profile of the frame 15. In a variant, other members, such as a gripping surface with small reliefs, can be used to prevent slipping or sliding of the bracket or a similar element 110.

[0269] The pipe holder can be an assembly for holding two pipes T so as to be arranged symmetrically with respect to the longitudinal direction X (i.e., the bag longitudinal axis A). Each symmetrical part is capable of holding one hose / pipe T.

[0270] Although Figure 4 and 6AEach shows a solution for horizontal storage, but it should be understood that thanks to the storage unit 10, the bag 2 can also be stored vertically or along any suitable direction. A sliding structure can be used to carry the protected bag (in the frozen state) by an annular frame or similar holding member, which can extend vertically for storage purposes.

[0271] Of course, for example Figure 6A-6B the fixing element 110 shown in can be used in an alternative where the frame 15 includes or holds one or more fastening members 146, 147, 148 for maintaining the sample unit SU and its bag 2' above the storage unit 10 parallel to the protection body reference plane P.

[0272] Filling of the bag

[0273] In, for example Figure 4 and Figure 6A several flexible bags 2 can be filled and protected in the system 1 shown. The housing can be formed by several stacked systems 1. When the flexible bags 2 in these systems 1 are stored on such a housing device, the flexible bags can be frozen, thawed, filled, or emptied simultaneously. When storing the flexible bag 2, the biopharmaceutical fluid / composition Q can be frozen or thawed. When shipping the flexible bag 2, generally, the biopharmaceutical composition Q is thawed, even though the biopharmaceutical fluid can also be frozen.

[0274] The flexible bag 2 can be inflated during the filling operation, which means that the circumference of the two main walls W1, W2 considered in the bag plane (corresponding to the protection body reference plane P) decreases due to the inward movement of different sides (also called the contraction stroke). Here, in the horizontal configuration of the system 1 as shown in Figure 4 or 6A, the four bag sides can be displaced inward due to vertical expansion (along the Z-axis).

[0275] Referring to Figure 1-3 , due to the lower flexibility of the material of the two plates 12A, 12B optionally provided with outer ribs, the bag expansion is restricted and controlled by the protection bodies 12, 112. The protection bodies 12, 112, 212 are made of a frost-resistant polyester or copolyester material that is not brittle at about 25°F or -4°C. This material is, for example, a stable copolyester of the PET or TRITAN TM type.

[0276] In some alternatives, the peripheral boundary 80 is regularly covered by positioning members PM, which are simply inserted onto the corresponding receiving parts of the elements including the attachment system 18. For example, two boss parts B12 protruding along the Z direction and two boss parts B12' protruding in the opposite direction along the Z direction form a group of four boss parts of the same receiving part that cooperate with the elongate positioning member PM.

[0277] In some variations, the attachment device or system 18 includes one or more traversing members or such boss portions B12, B12' configured to maintain the positioning member PM in an assembled state. In some alternatives, such traversing members may include insert parts IP( Figure 7A ) and associated fastening locks (e.g., mechanical locks such as nuts, bolts, etc.). Referring Figure 6B , such traversing members are engaged with a retaining effect through holes 18o that match slots or apertures 102 provided in plates 12A, 12B.

[0278] The traversing member is part of an attachment member that can be in a locked state. In the locked state, the traversing member cannot move or slide along the Z direction through the protective bodies 12, 112, 212 to prevent vertical separation of portions UP, LP of the positioning member PM. The same can optionally apply when having boss portions B12, B12' instead of traversing members.

[0279] Referring Figure 7A , the upper portion UP and the lower portion LP generally sandwich the peripheral boundary 80 in an area outside the clamping of the bag 2. Figure 7A Shows the initial position of the positioning member PM in the emptied state of the bag 2. A clearance is provided between each of the portions UP, LP and the inner or internal section 15a of the corresponding receiving profile to allow contraction.

[0280] Referring Figure 7B , it can be seen that the biopharmaceutical composition Q has been introduced into the flexible bag 2, and each of the positioning members PM can be shifted inwardly, possibly to a final position where the positioning member PM abuts inwardly against the adjacent edges BS, BS2 of the frame profile. In the filling configuration of the bag 2, each of the portions UP and LP may include front projecting portions 7, 7' that engage / extend through the inner (elongated) openings of the profile. Each front projecting portion 7, 7' of these portions UP, LP may have an inclined surface reaching a pressing surface in contact with the protective body 2 to form an inwardly open V-shaped section groove GS (distributed on both sides of the peripheral boundary 80 of the body). This groove GS can guide the expansion of the protective body near the peripheral boundary 80 to prevent the surfaces S, S' from directly contacting the frame 15 (thus preventing any contact against any profile edge / surface). This helps to protect the protective body material as the profiles 91, 92, 93, 94 typically employ more rigid materials such as steel, metal, or rigid plastic.

[0281] The two plates 12A, 12B are flexible enough to allow the protective body 12 to locally have a thickness greater than that of the circumferential region within or near the central region. Thus, when the biopharmaceutical fluid is frozen, the accommodation area / receiving portion 2r or the useful portion of the flexible bag 2, i.e., the inner region relative to the peripheral seal J, can be slightly bent. Accordingly, the dimension in the longitudinal direction (X) of the protective body 12 is slightly reduced. In this case, the biopharmaceutical fluid is slightly constrained by the two plates 12A, 12B.

[0282] Specific embodiment with a housing for storing a sample-containing bag

[0283] Reference Figure 5A-5B , the bag 2' may optionally be provided with hoses 104a, 104b and clamps, here two clamps associated with the two hoses 104a, 104b. Either of the hoses 104a, 104b can be formed as a closable conduit to allow filling or emptying of the bag 2'. Each clamp holds a hose 104a, 104b at a right angle respectively. One or more crimping rings CC are also provided, for example, between the clamp and the port 24' of the bag 2'. All these components can be accommodated within the internal volume V3 of the housing 130 together with the bag 2'.

[0284] The internal volume V3 is bounded by the side wall 131 of the housing 130 and extends between the bottom of the housing and the lid 35. The lid 35 is here a hinged lid connected to the side wall 131 by a hinge H35, which is typically a linear hinge. In the closed state, the lid 35 can be locked thanks to a snap fastener 35c that mates with an annular frame formed at or adjacent to the annular end of the side wall 131 (i.e., opposite the bottom of the housing). More generally, the housing 130 can be provided with a closing system that allows locking and unlocking of the lid 35 in the downwardly folded position, such a closing system preferably extending at a position opposite the hinge H35.

[0285] Typically, due to the hinged connection, the lid 35 cannot be separated from the other walls of the housing. The fastening elements 132, 133, 134 can be formed as arms or similar extensions protruding outward from the side wall 131. Thus, the lid 35 can be opened and closed without disturbing the fastening elements 132, 133, 134, which extend around an annular support for receiving the annular contact portion of the lid 35. The annular contact portion surrounds the central covering area of the lid 35, which covers the top open face defined by the side wall 131.

[0286] In Figure 4 and 10AIn the embodiment of -10B, the housing 130 is maintained at a vertical distance from the outer surface of the storage unit, i.e., at a vertical distance from the protection main bodies 12, 112. One or more snap buttons, clips, and / or similar detachable fastening members distributed on different sides of the frame 15 form the anchoring members of the housing fastening assembly.

[0287] Reference Figure 10B , it can be seen that a part of the fastening member, where the fastening members 147, 148 are formed by additional parts, is mounted on the frame 15 and extends upward from the engaging part (for engaging with the frame) to an upper fixed end for mating with an opening 136 or a similar attachment part provided in the fastening element 132 (see Figure 5A ). Another part of the fastening member, where the fastening member 146 is formed in the frame 15 and does not extend as high as the fastening members 147, 148. This difference in height level is compensated by one or more elongate tabs forming the fastening element 132, where each fastening element 132 is flexible and capable of tilting downward to reach the fastening member 146.

[0288] More generally, the fastening elements 132, 133, 134 can each be made of a plastic material that is more flexible than the plates 12A, 12B. Corresponding apertures 136 and 137, 138 can be provided at each of the fastening elements 132, 133, 134, in a distal position relative to the side wall 131. Such apertures 136 and 137, 138 provided in the region made of flexible material can easily cooperate with the corresponding protrusions provided in the frame 15 and / or on the outer surface of the top storage unit.

[0289] In some alternatives, at least two arms or tabs extending from the housing 130 in opposite directions form the fastening elements 133, 134, and the fastening elements can be inserted through the profiles 93, 94, for example, by sliding in grooves or similar recesses of such profiles 93, 94. Another fastening element 132 can then be fastened to the corresponding fastening member 146' formed on the protection main body 12. Such a fastening element 132 can prevent or limit further sliding, thus substantially locking the final attachment position of the sample unit SU. More generally, the housing 130 can be attached by sliding all or part of the fastening elements 132, 133, 134 into the frame 15. The frame 15 can be provided, for example, in two profiles 93, 94, where two longitudinal grooves or similar sliding parts extend parallel above the protection main body 12 and above any elongate opening in the inner section 15a for the passage of the peripheral boundary 80.

[0290] In some alternatives, at least two arms or tabs extending from the housing 130 in opposite directions form the fastening elements 133, 134 (see Figure 5A) The fastening element can be inserted through the profiles 93, 94, for example, by sliding in grooves or similar recesses in such profiles 93, 94 (where the grooves may be open at the axial ends). Another fastening element 132 can then be fastened to a corresponding fastening part 146' formed on the protective body 12 or to a corresponding fastening part 146' formed on the frame end. Such a fastening element 132 can prevent or limit further sliding, thus substantially locking the final attachment position of the sample unit SU.

[0291] Here, there is an optional part of the bag 2' that is flat and does not contain any biopharmaceutical fluid: the optional part can form a handle. Figure 5B and 6A In a non - limiting embodiment of and, the housing 130 is attached to the outer surface of the storage unit by one or more snap - fasteners, thereby forming the anchoring parts (136, 137, 138, 146', 147', 148') of the housing fastening assembly. Here, the rear longitudinal edge of the bag 2' (which is part of the handle) is shown to extend outside the housing 130 by protruding between the lid 35 and the housing frame. However, in a preferred alternative, the bag 2' can be fully accommodated inside the housing 130.

[0292] In an alternative using the anchoring protrusion or other anchoring part of the protective body, any self - locking can be provided to directly attach the housing 130 to the outer surface S, which here is the upper surface of the protective bodies 12, 112, 212. Similarly, any self - locking can be provided to attach the housing 130 to the frame 15 by extending as close as possible to the outer surface S (but usually with a small spacing gap).

[0293] Although the housing 130 is a parallelepiped here, its side walls 131 can have any prismatic shape with or without curved parts.

[0294] Furthermore, the side walls 131 of the housing 131 can be disposed outside the corner region CR of the protective bodies 12, 112, 212, and / or be held at a distance greater than 120 mm from the peripheral boundary 80 (i.e., from the reference plane). Figure 6A In an embodiment of, the housing 130 can be held attached to a backing region that remains substantially planar during the filling / thawing operation.

[0295] The housing 131 as a whole has a thickness that is less than the maximum thickness of the flexible bag 2 in the filled state. This also applies to the bag 2'. For example, the housing 131 has a thickness (measured along the Z - direction) of less than 50 mm or 60 mm. The overall thickness of the housing can be less than the distance along the Z - direction between the reference plane P of the protective body and the housing 130.

[0296] The fastening elements 132, 133, 134 can extend only from the side wall 131 in a direction away from the middle of the protection body 12 (away from the center C). All the interlocking or anchoring parts 136, 137, 138 provided in the fastening elements 132, 133, 134 are configured to contact the surface S at a distance greater than 200 mm or 500 mm from the center C (the center where the diagonal lines DL1, DL2 intersect) of the protection body 12.

[0297] Furthermore, it can be seen that the fastening elements 132, 133, 134 extend entirely above the protection body, such that they do not overlap with the sides of the frame 15. The fastening elements can thus be relatively short bands or tabs, such that the maximum extension of the sample unit in width or length cannot exceed the width of the frame 15.

[0298] Details of an exemplary embodiment for controlling bag inflation

[0299] In Figure 8 the embodiment, the reduction of the plate size (as considered in the XY plane) is obtained by the profile of the contraction stroke, and such reduction is adjusted to be different depending on the longitudinal positions of some positioning parts PM that locally prevent or limit such size reduction, for controlling the contraction stroke.

[0300] Here, the positioning parts PM (which are fastened to the peripheral boundary 80, as Figure 7A-7B shown) are longitudinally distributed, and some of the positioning parts are configured to limit the contraction stroke of the longitudinal sides of the protection body by a stopping effect generated due to the engagement of the positioning parts PM against the inner surfaces of the adjacent edges BS, BS2.

[0301] All or part of the positioning parts PM are stoppers for providing a stroke limit between the stoppers 41, 41', 42 and the adjacent surfaces BS, BS2 included in the frame 15 of the holding and retaining assembly HR. Referring to Figure 8 and 9A , the stoppers 41, 41' are arranged at or near the middle section MS of the bag 2 to generate a belt effect. In some embodiments, such a belt effect separates the two bulges or protrusions B1, B2.

[0302] Referring to 8 and 9A - 9B, the positioning parts can act as stoppers 41 or 41' only in the two middle parts 82 of the protection body 12. Therefore, since the stroke is allowed in the area closer to the corner region CR (here in the end part 81), the bag 2 covered by the accommodation protection body 12, 112 or 212 cannot form a single bulge or protrusion in its middle.

[0303] In addition, optional ribs prevent the formation of fold lines or hollows on the outer surface of the plate that would limit the good filling of the biopharmaceutical composition Q in the corner regions. Such ribs, which may have regions or portions of relatively low height (e.g., only at the diagonals DL1, DL2, since a guiding and folding effect has been obtained along the four sides of the rectangular protective bodies 12, 112), can contribute to the internal expansion of the protective bodies 12, 112 without creating hollows or improper fold lines that are detrimental to the filling in the corner region CR.

[0304] It should be understood that at a given filling level, the bag corners and the protective body corners can continue to move inwards during the filling operation, while the intermediate portion 82 is blocked by the stoppers 41, 41'. In the corner region CR, the contraction stroke is longer than in the middle, and at least the same liquid volume will be allowed to be stored compared to the case where no bulging / bowing is maintained.

[0305] Still referring Figure 8 , the stoppers 41, 41', 42 can be in predefined positions so as to form a positioning member PM. Here, compared to the distance of the stopper 42, only the stoppers 41, 41' positioned away from the end sides 120a, 120b have a relatively closer distance from the middle symmetry plane of the protective body 12. In Figure 8 such an alternative shown, such stoppers 41, 41', 42 follow the displacement (contraction) of the peripheral boundary 80.

[0306] During the filling operation, since the stoppers 41, 41' in the intermediate portion 82 of the longitudinal boundary portions 8a, 8b are (initially) offset inwards due to the arrangement of the attachment system 18 and / or due to the asymmetric placement of the positioning member, and since the abutment surfaces SB, SB2 are aligned parallel to the X direction, these stoppers 41, 41' come into abutment against the abutment surfaces SB, SB2 before the stoppers 42 adjacent to / facing the corresponding corner region CR. A bulging retention effect at the middle of the protective bodies 12, 112 is obtained.

[0307] In an alternative, ribs R1, R2, R3, R4 are provided in the plates 12A, 12B, and there may be corner ribs C1, C2 having a profile with a decreasing height towards the intersection regions of the diagonals DL1, DL2. In such an alternative, the retention effect is achieved by the regular expansion of the regions around the panel PP or PP1, PP2 (with a decreasing bulging effect near the center C in the intermediate region MR), thereby preventing the unwanted formation of obvious fold lines.

[0308] Of course, Figure 8This is only an exemplary embodiment for managing the shrinkage of boards 12A, 12B. More generally, the protection body 12 can be mounted to sandwich the flexible bag 2 and can be received / held in the gap of any suitable holding and retaining assembly HR, which is rigid and defines the outer circumference of the system 1. Depending on the filling level of the bag 2 sandwiched by the boards 12A, 12B, the protection body 12 can include one or more regions with a maximum thickness. To accommodate this thickness variation, the holding and retaining assembly HR can have an annular shape.

[0309] As Figure 9A-9B shown, one or more protrusions / bulges B1, B2 can be formed due to expansion control and early stop effects at the middle part (e.g., thanks to the early blocking stops 41 and / or 41'), such that the movement of the middle section MS is much less compared to the complementary sections covered by the parts of the protection body 12 near the first end side 120a and the second end side 120b.

[0310] More generally, any configuration with positioning components capable of forming stops away from the corner region CR can be provided, such that a higher restraint effect can be obtained at the center of the bag 2, as Figure 9A-9B specifically shown. This helps manage the freeze / thaw operations of the biopharmaceutical materials contained in the bag 2. This also helps stack, for example, Figure 4 and 6A the systems shown with better tightness (less vertical space between two adjacent storage units 10), thus providing the opportunity to store more bags 2 in the freezer.

[0311] Figure 9B The dashed lines in show such bulges that are typically obtained when allowing significant travel in each region of the peripheral boundary 80 similarly. This thus helps limit or prevent the displacement of the middle part of the protection bodies 12, 112, 212 in order to limit the accumulation blocks (with significant thickness) that may be difficult to thaw.

[0312] Figure 9A It is shown that any kind of holding part of the frame 15 or the assembly HR is suitable for allowing the protection bodies 12, 112, 212 to change their configuration (reduction of the body width and body length), thus allowing reduction of:

[0313] - the width of the bag 2 (w' < w, where w' is the width of the bag in the filled state, which is in contrast to the width w of the bag in the emptied state), and

[0314] - the length of the bag 2 (L' < L, where L' is the length of the bag in the filled state, which is in contrast to the length L of the bag in the emptied state).

[0315] In some variants, the positioning member PM can be positioned in the through slot and maintained fixed, for example, by fastening to the rigid frame 15 or a similar holding and retaining assembly or being integral therewith. The slots in the protection body can have larger dimensions only near the end sides 120a, 120b, thus allowing only a larger contraction at the corner region CR and preventing too large a bulge from forming near the center C (due to the bulging effect / holding in the middle part, where the positioning member is an early stop member).

[0316] The holding and retaining assembly HR can include at least three positioning members PM distributed on each of the longitudinal sides 120c, 120d, where typically one or two central stops 41 correspond to the positioning members PM arranged away from the corner region CR.

[0317] In addition to or independent of having such a bulging holding effect, each system or at least one system in the system stack can have a sample unit SU containing a sachet 2', in which a small amount representing the biopharmaceutical composition Q can be stored. In the thawing phase, it can help to have the sample unit SU provide a small amount of the biopharmaceutical composition Q, which has been subjected to the same processing, the same freezing operation as the composition contained in the large-capacity bag 2. The small amount has a faster heating rate, thus enabling a rapid thawing operation of the contents of the sample unit SU.

[0318] System 1 is very suitable for freezing, storing, and thawing biopharmaceutical materials contained in a flexible bag 2 with a simple concept. The storage unit 10 as described above can be protected by a tight peripheral part without disturbing the filling and expansion of the bag 2. Such a peripheral part or frame-like structure is of concern for at least one of the following reasons:

[0319] - Making the sample unit SU available at the same position as the bag (in the space typically defined by the frame 15) without complex handling,

[0320] - Effectively clamping the sample unit SU (mechanically clamping in some embodiments, typically without orifices / significant protrusions or creating defects in the protection body) to withstand a wide range of temperatures (without chemical bonding or without using an adhesive effect), preferably without attachments or large intermediate fixing parts,

[0321] - Regulating the biopharmaceutical composition Q with a high level of protection in an optimized volume.

[0322] In embodiments with adjustable positioning members PM, the filling of the bag 2 can be carried out with controlled and restricted expansion, such that the expansion is restricted in one or more regions where, without expansion control, the fluid thickness would reach a maximum. The internal volume or cavity defined by the main walls W1, W2 expands, thus preventing the intermediate regions of these walls W1, W2 from expanding freely. AsFigure 9A As shown, expansion can be restricted, especially along one or more waistlines BL joining two intermediate portions 82.

[0323] Due to the low or non-existent contraction stroke in the intermediate portion 82, indentations along such waistlines BL generally produce at least one notch. In the thus-filled bag 2 and in the receiving configuration of the storage unit 10, therefore, at least one notch is produced in the filled bag 2 between the two protrusions B1, B2. Since a more uniform thickness distribution is obtained, this allows for a substantially equal distribution of the fluid without reducing the capacity of the bag 2.

[0324] The bag 2 and the protective body 12 can be exposed to a temperature of about -70 °C or lower to freeze the biopharmaceutical fluid / composition Q. The annular shape of the frame 15 of the holding and retaining assembly HR helps to provide recessed areas through which cold air can circulate and flow between the systems 1 (even if they are fixed). However, other shapes and structures can be used to form a holding and retaining assembly for controlled expansion so that:

[0325] - Eliminate or reduce the formation of excessive protrusions during freezing,

[0326] - Allow the sample unit SU to be attached parallel to the substantially flat protective bodies 12, 112, 212, regardless of the filling level of the bag sandwiched by the plates 12A, 12B.

[0327] The invention has been described in connection with preferred embodiments. However, these embodiments are merely exemplary and the invention is not limited thereto.

[0328] Of course, the bag 2 of the present invention is not in any way limited to a bag having four sides and / or a bag wider than its width. The bag 2 can have other shapes with two substantially parallel sides, covered by a pair of plates 12A, 12B or a similar protective body comprising two flat portions. Although each plate 12A or 12B is shown as an integral element, alternatives can be used to combine two or more flat receiving parts capable of constraining the expansion of the bag 2, while being more or less displaceable for adjusting the contraction stroke.

[0329] Those skilled in the art will understand that other variations and modifications can be readily made within the scope of the claimed invention.

[0330] For example, although the fastening elements 132, 133, 134 have been shown as extensions of the housing 130, one or more of such fastening elements can alternatively be included in a tab or extension integral with the bag 2'. In addition to or instead of the housing 130, a protective layer or overwrap integral with the bag 2' (i.e., the overwrap covers or wraps the bag 2' in contact with the product) can also be optionally provided.

[0331] Any reference signs in the appended claims shall not be construed as limiting the claims. It will be obvious that the use of the verb “to comprise” and its conjugations does not exclude the presence of any other elements than those defined in any claim. The indefinite article “a” or “an” preceding an element does not exclude the presence of a plurality of such elements.

Claims

1. A freeze / thaw containment system for containing a biopharmaceutical composition, which comprises: - A flexible bag having a first capacity, which is configured to contain the biopharmaceutical composition; - A storage unit for freezing, storing, and thawing the biopharmaceutical composition contained in the flexible bag; - A pouch having a second capacity, which is configured to contain a composition representing the biopharmaceutical composition, the second capacity being lower than the first capacity; and - A housing that defines an internal volume for accommodating the pouch in a filled state; wherein the storage unit comprises: - A protective body including two plates for protecting the flexible bag, the protective body including a longitudinal axis and having four sides, the four sides including two longitudinal sides extending parallel to the longitudinal axis and two other sides, the two other sides including a first end side and a second end side each perpendicular to the longitudinal axis, and - Attachment means for fastening the two plates such that in an assembled state of the two plates, the protective body includes a peripheral boundary extending annularly in a protective body reference plane, the peripheral boundary having at least one opening capable of receiving at least one port of the flexible bag, wherein the system further includes a rigid peripheral portion adjacent to or overlapping the peripheral boundary, the rigid peripheral portion having a mounting kit including three separate support members for supporting the protective body, wherein in the assembled state: - The protective body extends planar along the protective body reference plane in an emptied state of the flexible bag; - The two plates respectively form a lower surface and an upper surface of the protective body, and at least one of the lower surface and the upper surface is an outer surface of the storage unit; and wherein the housing includes at least two fastening elements that cooperate with a fastening member included in one of the mounting kit and the outer surface of the storage unit so as to fasten the housing along the storage unit, substantially parallel to the protective body.

2. The freeze / thaw containment system according to claim 1, wherein, the two plates are flexible to allow the protective body to have a greater thickness in a central region than in a circumferential region with respect to the protective body reference plane, the thickness being measured between the lower surface and the upper surface in a direction perpendicular to the protective body reference plane.

3. The freeze / thaw containment system according to claim 1, wherein, the flexible bag is directly sandwiched between the two plates, and the two plates constrain the flexible bag.

4. The freeze / thaw containment system according to claim 3, wherein, the two plates are two parts.

5. The freeze / thaw containment system according to claim 1, 2, 3, or 4, wherein, the fastening members are distributed: in a first zone adjacent to a first side of the two longitudinal sides, and in at least one second zone located away from the first side.

6. The freezing / thawing containment system according to claim 1, 2, 3 or 4, characterized in that, the rigid peripheral part is a frame having a top face extending above the protection body and a lower face extending below the protection body, wherein the housing is detachably fastened to the mounting kit that extends around three sides of the flexible bag, and the fastening members include: - two fastening members distributed on the two longitudinal sides, the two fastening members extending entirely above the protection body and away from the two other sides; and - at least one fastening member integrally formed with one of the three individual support members or with a corner section interconnecting two of the three individual support members.

7. The freezing / thawing containment system according to claim 1, 2, 3 or 4, characterized in that, the fastening members distributed on the frame including the three individual support members are configured for interlocking of the housing.

8. The freezing / thawing containment system according to claim 1, 2, 3 or 4, characterized in that, two of the fastening members are integrally formed with two individual corner sections so as to be distributed on the frame around the flexible bag.

9. The freezing / thawing containment system according to claim 7, characterized in that, the housing has a prismatic shape.

10. The freezing / thawing containment system according to claim 8, characterized in that, the housing has a parallelepiped shape and includes: - a housing frame that defines a housing opening for accessing the internal volume of the housing; and - a lid configured to detachably close the housing opening.

11. The freezing / thawing containment system according to claim 1, 2, 3 or 4, characterized in that, the bag is part of a bag unit that includes one or more openings or ports, at least one of the one or more openings or ports being formed as a closable conduit to allow filling or emptying of the bag, and wherein the bag and the closable conduit are stored in the internal volume of the housing.

12. The freezing / thawing containment system according to claim 10, characterized in that, the bag is part of a bag unit that includes one or more openings or ports, at least one of the one or more openings or ports being formed as a closable conduit to allow filling or emptying of the bag, and wherein the bag unit is housed in the internal volume in the closed state of the lid.

13. The freezing / thawing containment system according to claim 7, characterized in that, the housing has a lower face that: faces the outer surface of the storage unit and extends parallel to the protection body reference plane in the emptied state of the flexible bag.

14. The freezing / thawing containment system according to claim 7, characterized in that, the housing is made of a sheet of transparent plastic material.

15. The freezing / thawing containment system according to claim 1, 2, 3 or 4, characterized in that, the housing includes: - side walls that define the internal volume; and - Two opposite tabs, each having a base connected to said side wall, each of said two opposite tabs being part of said fastening element.

16. The freezing / thawing containment system according to claim 1, 2, 3 or 4, further comprising: - A pipe connected to said flexible bag and configured to allow the liquid of said biopharmaceutical composition to flow; - A pipe holder for holding said pipe; and - A frame with four sides forming said rigid peripheral part, said frame intersecting with and extending parallel to said protection body reference plane, said frame being configured to directly or indirectly hold said protection body, at least two profiles being included in said frame to form all or part of said four sides; wherein said pipe holder includes at least one fixing element elastically mounted on one of said at least two profiles and having a clamping part for holding said pipe.

17. The freezing / thawing containment system according to claim 16, characterized in that said at least one fixing element has one of said fastening members adjacent to and / or superimposed on said clamping part.

18. The freezing / thawing containment system according to claim 1, 2, 3 or 4, characterized in that said fastening member is formed as a coupling part of said mounting kit and is inserted between: - A support part of said rigid peripheral part, - And said fastening element of said housing.

19. The freezing / thawing containment system according to claim 1, 2, 3 or 4, characterized in that the housing fastened along said storage unit has a housing thickness measured perpendicular to said protection body reference plane, and said housing thickness is less than the distance between said bag and said protection body reference plane.

20. A method of assembling the freezing / thawing containment system according to claim 1, said freezing / thawing containment system being a protection system for storing said biopharmaceutical composition contained in said flexible bag of said freezing / thawing containment system and withstanding freezing and thawing of said biopharmaceutical composition, said flexible bag having a first capacity, said method comprising: - Selectively sandwiching said flexible bag between said two plates of a protection body by covering parts distributed in two plates for covering said flexible bag, said protection body being configured to protect said flexible bag and including said two plates, said protection body further having a longitudinal axis and including four sides, said four sides including two longitudinal sides extending parallel to said longitudinal axis and two other sides, said two other sides including a first end side and a second end side each perpendicular to said longitudinal axis; - Using an attachment device to fasten said two plates such that in the assembled state of said two plates, said protection body includes a peripheral boundary extending annularly around said covering part, said peripheral boundary having at least one opening for receiving at least one port of said flexible bag; and - Provide a housing that defines an internal volume in which the bag extends in a filled state, the bag having a second capacity and containing a composition representing the biopharmaceutical composition, the second capacity being lower than the first capacity, wherein the protection body and the attachment means belong to the storage unit, wherein the assembled state is obtained after configuring the two plates to sandwich the flexible bag and after attaching the housing to the fastening member, the fastening member belonging to a rigid peripheral portion surrounding the protection body or to the outer surface of the storage unit formed by the protection body, and wherein in the assembled state, the two plates respectively form the lower surface and the upper surface of the protection body, at least one of the lower surface and the upper surface being the outer surface of the storage unit, the housing facing the outer surface of the storage unit and having at least two fastening elements that cooperate with the fastening member so as to maintain and fasten the housing along the storage unit, parallel to the protection body.

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