Freeze / thaw containment system for flexible pouches filled with biopharmaceutical fluids and method of assembling the freeze / thaw containment system using a protective body portion - Patents.com

Abstract

A freeze / thaw containment system is provided, which includes a protective body and a flexible pouch of a first volume protected by two plates of the protective body. The two plates are attached together at a peripheral margin to form a rectangular protective body. The peripheral margin is mounted within a stationary frame and is allowed to be displaced inward during filling of the pouch, while the protective body extends generally planarly to clamp and restrain the pouch. One of the stationary frame and the protective body includes a fastening member for attaching a casing configured to store the bag, such that the bag is fastened parallel to the protective body. Two fasteners for cooperating with the fastening member are distributed around a bag containment part of a second volume, which is at most one-tenth the first volume. The same biopharmaceutical composition is contained within the pouch and the bag.

Description

[Technical field]

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

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

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

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

[0005] Document EP2322442 discloses a container for flexible pouches. The container comprises a lower part and an upper part, which are rigid and joined along a common edge, which forms a single-piece container. The container has a volume much more significant than the volume of the flexible pouch. As a result, the container has a useless volume. Moreover, if the flexible pouch is not sustained by suitable positioning means provided in the container, it may be displaced in the container, especially during shipment. Thus, the risk of leakage increases.

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

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

[0008] Document US 2018 / 125757 provides a protective body part, such that a flexible pouch is sandwiched by two plates of the protective body part with a restraining effect. A freeze / thaw protection system can be obtained by combining such a protective body part and a single-use flexible container wrapped by a protective shell. However, uniform fluid distribution can be difficult because in the filled state of the flexible container, a significant bulge (large belly) is formed in the middle part. Therefore, in the frozen state, the expansion of ice is relatively significant, and more time is required to freeze this large mass in the middle part of the internal volume of the pouch.

[0009] Moreover, for large volume flexible containers, it becomes interesting to obtain / use small volumes of products stored in pouches without complex operations and without causing an increase in the bulk of the system. [Prior art documents] [Patent documents]

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

[0011] The objective of the present invention is to provide a storage unit to obtain a robust freeze / thaw containment and protection system that is efficient to prepare large amounts of biopharmaceutical materials in flexible pouches of flexible design (typically 2D pouches that expand in the filled state), while also allowing to use all or part of the system as a backing / support part for enhanced integration of functionality, making the system user-friendly. [Means for solving the problem]

[0012] To this end, an embodiment of the present invention is a freeze / thaw containment system for storing a biopharmaceutical composition, the freeze / thaw containment system comprising: - a flexible pouch of a first volume configured to store a biopharmaceutical composition; - a storage unit for use in freezing, storing, and thawing a biopharmaceutical composition contained in a flexible pouch; - a bag of a second volume configured to store a composition representative of a biopharmaceutical composition, the second volume being less than the first volume; - a casing defining an inner volume for containing the bag in its filled state; Including, The storage unit is - a protective body including two plates for protecting a flexible pouch, 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 including a first end side and a second end side respectively perpendicular to the longitudinal axis; - a mounting device for fastening two plates, such that in the assembled state of the two plates the protective body part comprises a peripheral margin extending annularly in a reference plane of the protective body part; Including, The system further includes a rigid peripheral part, the rigid peripheral part being adjacent to or overlapping the peripheral margin, the rigid peripheral part being provided with a mounting set including three separate support members for supporting the protective body portion; In assembled state: - the protective body portion extends planarly along a protective body portion reference plane in an empty state of the flexible pouch; - the two plates respectively form (i.e. include) a lower surface and an upper surface of the protective body part, at least one of the lower surface and the upper surface being a storage unit outer surface; A freeze / thaw storage system is provided in which the casing includes at least two fastening elements that cooperate with fastening members provided / contained in the mounting set and one of the storage unit outer surfaces to enable the casing to be fastened along the storage unit parallel to the protective body portion.

[0013] Thus, the sample is easily available thanks to the sample unit or bag. The bag can be easily attached to the protective body thanks to the removable fasteners, the casing typically extending away from the intermediate part of the protective body along the storage unit outer surface. This is of interest to improve compactness, since when the flexible pouch stores more than 50L or 75L, the thickness can be significantly larger in such intermediate parts compared to the thickness near the surrounding parts of the protective body. If required, the bag can also be kept attached to the protective body during transport in freeze / thaw operations without increasing the bulk of the system in the filled state of the pouch.

[0014] The bag is advantageously protected by a casing if the system must be transported (in some cases the biopharmaceutical composition is transported in a frozen state), thus forming a sample unit and providing a way to rapidly analyze or test the composition, since the contents of the small bag are much faster to thaw and retrieve at a homogenous positive temperature compared to the contents of a pouch having a relatively large volume.

[0015] The bag and storage unit are supported together by a support member, which defines all or part of the peripheral rigid parts.

[0016] Typically, the casing may extend above the storage unit outer surface formed by the upper plate of the two plates, possibly without contact between the casing and the protective body. Optionally, all fastening members are provided in the mounting set, preferably completely above the protective body.

[0017] The storage unit can simultaneously have an expandable part for expansion along the vertical direction (Z direction) as a function of the filling of the pouch, and a rigid sliding part (fixed non-displaceable along the Z direction) formed as an interface for insertion into a frame (typically annular frame) or any similar part that surrounds the pouch and cooperates with the peripheral margin of the protective body part. The expandable part is composed of the protective body part (typically following the expansion of the pouch, with a restraining effect that limits the vertical elongation of such expansion).

[0018] According to another option, the casing can be in contact (direct contact) with the storage unit outer surface, possibly without the use of an intermediate fastening device or intermediate adhesive layer. One of the plates holds the casing, with the protective body acting as a backing assembly for the casing.

[0019] The bag can be configured to contain the same composition as in the flexible pouch to form the sample.

[0020] The peripheral margin may be provided with at least one opening capable of receiving at least one port of the flexible pouch, which may be of interest in order to allow the pouch to be filled or emptied. The opening or port may be formed, for example, as a closable tube and may be provided between the facing parts of the weld joint where the two constituent sheets of the pouch are joined. Such an opening may be of interest in order to allow the pouch to be filled or emptied.

[0021] Optionally, two of the fastening members are integrally formed with two separate corner sections and are distributed on the frame around the flexible pouch. Such an arrangement allows the bag to be stored near the end part of the system without interfering with the location of the tube where the fastening members may be connected to the pouch. Typically, the corner section with the fastening members is away from any open side of the peripheral margin.

[0022] The peripheral part can be a frame with four corner sections interconnecting the frame profiles, the peripheral margin having only one open side located between two corner sections, which two corner sections are at the end opposite to the end having the two corner sections provided with fastening members for fastening the casing.

[0023] According to an embodiment, the two plates are sufficiently flexible to allow the protective body to have a greater thickness in the central area than in the peripheral areas, relative to a protective body reference plane, the thickness being measured between the lower and upper surfaces along a direction perpendicular to the protective body reference plane.

[0024] According to an embodiment, the flexible pouch is directly clamped between two plates that restrain the flexible pouch. The flexible pouch is typically more flexible than the material of the protective body. The restraining effect is of interest for the step of emptying the flexible pouch and is also advantageous to limit the expansion of the fluid (vertical expansion when the protective body extends generally horizontally such that the protective body reference plane extends substantially horizontally), especially during freezing.

[0025] The casing may be made from a plastic material that is harder than the plastic material of the flexible pouch.

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

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

[0028] Optionally, several protective body through slots are provided, longitudinally distributed in each of the two opposing margin portions.

[0029] The attachment devices may interact with some of the protective body through slots or may be distributed in alternating locations relative to the protective body through slots.

[0030] In some embodiments, each of the two plates includes an embossing which, in an assembled state of the plates to form the protective body, defines several protective body embossings protruding in a first direction perpendicular to the protective body reference plane, which form corresponding cavities opening in a second direction opposite to the first direction, the embossings being distributed longitudinally at the peripheral margin.

[0031] A plurality of embossments may be provided in one of the two plates and may engage an equal number of corresponding cavities provided in the other of the two plates.

[0032] Independently of whether the system has a bag held by a protective body or by a frame or similar peripheral part (possibly via a casing), the system: - a tube connected to the flexible pouch and configured for liquid flow of the biopharmaceutical composition; and - a frame provided with four sides, the four sides forming the rigid peripheral part of the system and extending parallel to a protective body reference plane, at least two profiles contained in the frame forming all or part of the four sides, the four sides being preferably formed by four profiles; - a tubing holder for holding a tube, the tubing holder comprising at least one fastening element, the at least one fastening element being elastically mounted on one of the profiles and provided with a clamping part for holding the tube; It is possible to include:

[0033] Typically, the frame intersects and extends parallel to the protective body reference plane, and the frame is configured to directly or indirectly hold / support the protective body.

[0034] In some embodiments, the tube forms a port of the flexible pouch. Moreover, the tubing holder may be distributed in two locations, with two separate and spaced apart fixation elements.

[0035] In some embodiments, at least one fixing element is provided with one of the fastening members (for the sample unit), which is adjacent to the clamping part and / or superimposed on the clamping part.

[0036] In a variant, one of the four sides is constrained so that the frame comprises three profiles extending parallel to the protective body reference plane.

[0037] The fixing element may have a U- or C-shaped section with an internal surface for engaging with three sides of a profile (receiving profile) that is part of the frame. The clamping part may be separate from the U- or C-shaped section. The clamping part may be formed on an external surface of the fixing element, possibly defining a C-shaped receiving portion, - it protrudes from the outer face of the bracket (fixing element) and / or - It faces away from the acceptance profile.

[0038] In various embodiments of the system, optionally, one or more of the following arrangements may be relied upon: - The two plates are in two pieces. The two plates may have the same thickness, lower than 2 mm, and each of the two plates may have a density of 1.10 g / cm 3 and is made from a plastic material. The two plates are made from the same plastic material, preferably transparent or translucent. - The protective body is made from a freeze-resistant polyester or copolyester material that is not brittle at approximately 25°F or -4°C. - The material of the protective body is PET. - The protective body material is TRITAN (i.e., a copolyester compound called TRITAN™, which is a transparent, amorphous thermoplastic material that is typically made by combining three monomers; some formulations of this material contain no additives, while others contain about 10% or less of additives). - The protective body material is an amorphous copolyester made by combining the following monomers: dimethyl terephthalate, 2,2,4,4-tetramethyl-1,3-cyclobutanediol, and 1,4-cyclohexanedimethanol. - The protective body part is directly engaged by a positioning member belonging to the mounting device, so as to have a shrinkage profile at the periphery of the protective body part, and in some cases, at the margin parts, the shrinkage due to the direct engagement of the positioning member engaged in the intermediate region of the protective body part is hardly reduced or is less. The positioning members are distributed around the covering part. - The holding and sustaining device has two separate protective parts, the two separate protective parts being interlocked by a positioning member such that the protective body part is clamped between the two protective parts and such that the protective body part is positioned within a gap bounded by the two protective parts. - the holding and sustaining devices comprise, for example, profiles with a U-shaped or C-shaped cross-section, each defining an internal cavity, the positioning members being respectively arranged inside one of the respective cavities of the holding and sustaining devices and having a positioning member selectively movable inwardly according to a stroke that depends on the clearance provided inside the cavity, such that when an abutment surface belonging to a given positioning member abuts against an abutment edge or abutment face of the profile that accommodates the given positioning member, the positioning member acts as a stopper for limiting the expansion of the protective body part. - each of the positioning members is engaged to extend through one of the two opposing margin portions by extending through at least one cut or recess formed in one of the two margin portions; - the protective body plane intersects with four marginal portions, the four marginal portions being distributed in a rectangular shape and respectively in contact with two protective parts of the shell, the four marginal portions being arranged around the covering portion, the two opposite marginal portions being part of this group of four marginal portions. In various embodiments, the system may be provided with one or more of the following features: The fastening members are distributed in different (spaced) areas. - The fastening members are distributed in a first region adjacent to a first of the two longitudinal sides of the protective body portion and also in at least one second region positioned away from the first side. - The casing is removably fixed to the surrounding part (frame). - the peripheral part includes a covering part covering the peripheral margin, and the fastening member is formed as a coupling piece of a mounting set; a similar rigid component / support of the profile or surrounding part (to support the protective body part); Casing fastening elements and It is interposed between. The rigid peripheral part is a frame having an upper side extending above the protective body part and a lower side extending below the protective body part. The casing is removably secured to the protective body part. The casing is removably secured to a mounting set, the mounting set extending around three sides of the flexible pouch. - the fastening members include two fastening members distributed on two longitudinal sides, the two fastening members extending completely above the protective body part and extending away from the two other sides. - The fastening members include at least one fastening member that is integrally formed with one of the three separate support members or that is integrally formed with a corner section that interconnects two of the three separate support members. - The casing is secured to the outer surface of the storage unit by one or more snap buttons. - The fastening members are distributed over a frame comprising three separate support members and configured for the interlocking of the casing. - Fastening members provided on the outer side of the storage unit are configured for interlocking of the casing. The interlocking of the casing may be obtained by positive locking of male projections into corresponding recesses, like snap buttons or similar projecting members for positive locking in corresponding recesses. At least one of the male protrusions may be formed / included in one of the support members. At least one of the recesses may be formed / contained in one of the support members. - at least one of the recesses may be formed / contained directly in one of the two plates (i.e. without any additional material covering the constituent layers of the plates) (if such a recess opens inwards, an outwardly projecting member may be generated; conversely, if such a recess opens outwards, an outwardly projecting member may be generated). The casing is typically fixed to the storage unit outer surface or mounting set without any adhesive layer or any adhesive means. - the casing is made from at least one piece completely separate from the protective body part and from the frame forming the rigid peripheral part, such that the casing is completely removable so as to be separated from the protective body part. - The casing has a prismatic shape. - The casing has a parallelepiped shape. The casing is provided with a casing frame which delimits a casing opening for access to the inner volume of the casing. The casing has a lid configured to close the casing opening in a removable manner (the lid partly bounds the inner volume). In the protective body part, the two other sides are the short sides of the protective body part compared to the longitudinal sides. - the casing is elongated (when fixed to the peripheral parts and / or the protective body part) in a direction parallel to the two short sides of the storage unit. Each of the two plates is a plate having a rectangular shape with four corners and two imaginary diagonals that each intersect at a pair of corner vertices of the four corners. - the side walls of the casing are intersected by only one of the two imaginary diagonals and are located away from the intermediate part of the protective body. the side wall portion may be located entirely within a gap bounded by two segments of the two imaginary diagonals without being intersected by any one of the two imaginary diagonals. - The thickness (or height) of the casing is below 50mm or 60mm, such thickness or height being typically measured between the bottom wall and the lid of the casing. The casing has a length which may be lower than the width of the protective body part and may be comprised between 200 mm and 1200 mm, for example between 320 mm and 950 mm. - A bag is part of a bag unit that contains one or more openings or ports. At least one of the opening ports is formed as a closable tube, allowing the bag to be filled or emptied. - The bag and the respective closeable tube are stored within the inner volume of the casing. The bag unit is contained within the inner volume in the closed state of the lid. The casing has a lower side which faces the outer surface of the storage unit and which extends parallel to the protective body reference plane in an empty state of the flexible pouch. - The casing has a contact surface which is in contact with the outer surface of the storage unit (when the casing is fixed to the peripheral part and / or the protective body part). The contact surface may extend parallel to a reference plane of the protective body part in an empty state of the flexible pouch. - the casing fastened along the storage unit has a smaller size, which corresponds to a casing thickness measured perpendicular to the protective body reference plane, the casing thickness being less than the distance between the bag and the protective body reference plane. The support member also supports a tube connected to the port (the tube is typically an integral part of the pouch), preferably so that the tube extends between the peripheral part and the bag. - The casing is made from one piece of clear plastic material. The casing lid is a hinged lid. The casing is provided with a hinged lid which is movable relative to the annular frame which defines a casing opening for access to the inner volume. The lid extends in a plane parallel to the reference plane of the main body. - The hinged lid is rotatable about a linear hinge. The fastening element includes at least one tab formed as an extension from a side wall of the casing on a side opposite the linear hinge. - The bag may comprise two plastic sheets (of a liquid impermeable material) bonded together to form the bag. - The bag has two sheets that are welded together, each having an inner surface for direct contact with the composition stored within the bag. The two sheets may be made of a transparent plastic material suitable for contact with the biopharmaceutical composition. The casing includes a side wall that defines an inner volume. The casing further includes two opposing tabs each having a base connected to the side wall portion, each of the two opposing tabs being part of a fastening element. - the storage unit includes a slide part, which is supported by a peripheral margin and is formed as an interface with the holding and sustaining assembly, the slide part including a positioning member, which is engaged with and / or clamps the peripheral margin, while the holding and sustaining assembly includes two longitudinal covering parts each extending parallel to the protective body reference plane. - The interface with the retaining and sustaining assembly prevents the four protective body margin portions from sliding inward (towards its intermediate part) beyond the stop parts or rim portions (forming at least one abutment surface) of the retaining and sustaining assembly. - The two plates are configured to clamp the flexible pouch in order to restrain the flexible pouch in its filled state, and the protective body part is deformable and movable within two gaps respectively bounded by two longitudinal covering parts of the holding and sustaining assembly, allowing the two plates to move, extend and contract in a transverse direction belonging to the protective body part reference plane.

[0039] According to a particular feature, at least one of the two plates is provided with outwardly projecting ribs for local structuring of the protective body, at least in a peripheral area around the intermediate part of the protective body, All or part of the fastening elements are - in an area contained within one of the ribs, and - at a given distance from the intermediate part, In contact with the exterior surface of the storage unit.

[0040] In some variations, the fastening elements are provided entirely on the outside of the ribs.

[0041] According to another embodiment, a freeze / thaw containment system for storing a biopharmaceutical composition has two plates forming a first surface and a second surface of a protective body, respectively, at least one of the first surface and the second surface is a storage unit outer surface (the storage unit outer surface is formed in an overlapping configuration with a receiving portion of a flexible pouch for receiving the biopharmaceutical composition), one of the storage unit outer surface and a mounting set covering a peripheral margin of the protective body is provided with a fastening member, the fastening member is disposed above a reference plane of the protective body and faces upward; At least one of the bag and a casing configured to store the bag is provided with at least one fastening element, which cooperates with the fastening member to fasten the bag parallel to the storage unit, and the at least one fastening element is arranged or distributed around the storage part of the bag.

[0042] The at least one fastening element can include two or more fastening elements distributed around a storage part, the storage part defining a second volume (lower than the first volume).

[0043] In some embodiments, the bag is provided with fastening elements and is attached directly to the fastening members on the surface of the storage unit (such that the bag can be attached without being stored in a casing). Typically, the bag may be provided with at least two fastening elements that cooperate with the fastening members to allow the bag to be fastened to the protective body.

[0044] In some embodiments, the two fastening elements are integral with the storage part of the bag.

[0045] In some embodiments, the two fastening elements are removably attached to the storage part of the bag.

[0046] In some embodiments, the two fastening elements are non-removably attached to the storage part of the bag.

[0047] The containment part of the bag may be formed from only two sheets of plastic material (typically a clear plastic material).

[0048] The fastening elements extend beyond the annular weld seam that separates the containment part from the surrounding parts of the bag.

[0049] At least one tube for filling and / or emptying the storage part belongs to the peripheral part of the bag.

[0050] The bag is provided with a plurality of fastening elements, at least one of which maintains the bag tube along with the protective bag in a predetermined position when secured to one of the fastening members or when secured to an auxiliary mounting device of the storage unit.

[0051] According to another aspect, there is provided a method for assembling a freeze / thaw containment system according to the invention, the freeze / thaw containment system being a protective system for storing and withstanding freezing and thawing of a biopharmaceutical composition contained within a flexible pouch of the freeze / thaw containment system. The method comprises: - sandwiching the flexible pouch between two plates of a protective body part with a covering portion selectively distributed among the two plates to cover the flexible pouch, the flexible pouch being of a first volume, the protective body part being configured to protect the flexible pouch and comprising two plates, the protective body part further having a longitudinal axis and comprising four sides, the four sides comprising two longitudinal sides extending parallel to the longitudinal axis and two other sides comprising a first end side and a second end side respectively perpendicular to the longitudinal axis; - using a mounting device for fastening the two plates such that in the assembled state of the two plates the protective body part includes a peripheral margin extending annularly around the covering portion in a protective body part reference plane, the peripheral margin being provided with at least one opening for receiving at least one port of the flexible pouch; - providing a casing defining an internal volume, a bag in a filled state extending into the internal volume, the bag being of a second volume and containing a composition representative of a biopharmaceutical composition, the second volume being lower than the first volume; Including, The casing has at least two fastening elements that cooperate with complementary fastening members provided on the outer surface of the protective body so that the casing is maintained and fixed to the protective body. Typically, the protective body and the mounting device belong to a storage unit. The assembled state is obtained after configuring the two plates to clamp the flexible pouch and after fixing the casing to fastening members belonging either to a rigid peripheral part surrounding the protective body or to the outer surface of the storage unit formed by the protective body.

[0052] In the assembled state, the two plates form lower and upper surfaces, respectively, of the protective body part, at least one of the lower and upper surfaces being an outer surface of the storage unit, and the casing faces the outer surface of the storage unit and has at least two fastening elements which cooperate with the fastening members so as to maintain and fix the casing along the storage unit, parallel to the protective body part.

[0053] In some embodiments, the fastening region extends a certain distance of the perimeter area over which the attachment device can extend, which is of interest in order to have a compact solution.

[0054] The storage unit may be supported by a rigid outer frame surrounding the periphery of the protective body and / or the periphery of the flexible pouch, the outer frame defining the external periphery of the system. The casing may extend completely within the periphery limits of the rigid outer frame. The casing may optionally extend above the protective body without contact between the storage parts of the casing and this frame, and may extend between two elongated profiles belonging to the frame.

[0055] In some embodiments, the casing in the fastened state does not interfere with the displacement and contraction of the marginal portions of the plates during the filling step because the casing extends a predetermined distance from the frame or similar holding and sustaining assembly.

[0056] In some options, the flexible pouch is expanded upon filling the flexible pouch with the biopharmaceutical composition in a fluid state, and each positioning member movable to reach the abutting condition while guided within a frame or similar holding and sustaining assembly is configured to constrain the middle of the flexible pouch more than the two opposing ends of the flexible pouch. In some options, this constraining effect results from a relatively low relative displacement between the first positioning member and the first protective body through slot or embossment interacting with the first positioning member, as compared to the displacement permitted at and / or near the corners of the protective body, the first protective body through slot or embossment being provided at an intermediate position in each of the two opposing protective body margin portions.

[0057] Typically, the clearance range may be sufficient to still allow each end part of the protective body portion to be moved inwardly due to freezing of the aqueous liquid stored in the pouch (i.e., due to water expansion as it freezes) in a filled state of the pouch clamped by the plates.

[0058] The contents of the bag stored within the casing and the contents of the flexible pouch can typically be frozen simultaneously without displacing / removing the casing from its storage position (where it is affixed to the outer surface of the protective body portion).

[0059] Other characteristics and advantages of the present invention will become apparent to those skilled in the art during the course of the description that follows, given by way of non-limiting example with reference to the attached drawings, in which: [Brief description of the drawings]

[0060] [Figure 1] FIG. 1 is a perspective view of a storage unit according to a first embodiment of the invention, before the two plates of the protective body are assembled. [Diagram 2] FIG. 2 is a top view of the assembled storage unit of FIG. 1, in which a ribbed pattern is provided on the protective body upper surface, including fastening members for directly or indirectly securing a bag thereto. [Diagram 3] FIG. 1 illustrates a freeze / thaw storage system in which a flexible pouch, in its empty state, is sandwiched between two plates forming a protective body portion, while a peripheral margin of the protective body portion is sandwiched between positioning members. [Figure 4] FIG. 1 is a perspective view showing a freeze / thaw system using a peripheral frame housing internal positioning members in a filled configuration in which the positioning members are inactive to limit inward movement and contraction of the plates that clamp the flexible pouches. [Figure 5A]FIG. 2 is a perspective view of a first exemplary casing for housing a bag, provided with fastening elements around the side walls of the casing; [Figure 5B] FIG. 2 is a perspective view of a second exemplary casing for housing a bag, the casing being provided with fastening elements around its side walls. [Figure 6A] FIG. 5 is a perspective view similar to FIG. 4, but with some of the internal positioning members adjusted to selectively limit the displacement and contraction of the plate in an intermediate region of the protective body, and the plate being provided with a ribbed pattern. [Figure 6B] FIG. 6B is a perspective view of a detail of the system of FIG. 6A showing a portion of a tubing holder engaged on a frame of the system. [Figure 7A] A vertical cutaway view showing a positioning member suitable for forming a stopper, configured to slide inwardly into the profile cavity with a limited stroke while retaining a portion of the peripheral margin of the protective body portion. [Figure 7B] FIG. 7B is the same vertical cutaway view as FIG. 7A, showing the abutment position, where the positioning members have stopped inward movement of corresponding peripheral margin portions of the protective body portion. [Figure 8] A figure illustrating details of an exemplary distribution of positioning members provided to hold / maintain the same longitudinal sides of the peripheral margins of the protective body portion, making it possible to limit the bulging effect in the middle region of the storage unit in the filled state of the flexible pouches. [Figure 9A] 9 is a top view of a liquid-filled flexible pouch inside the system of FIG. 8, without showing the protective body portion and positioning member. [Figure 9B] 9 is a side view showing a frame-like holder and flexible pouch filled with liquid inside the system of FIG. 8, without showing the protective body portion and positioning member. FIG. [Figure 10A]FIG. 2 is a perspective view of a freeze / thaw containment system capable of supporting and mounting a sample unit, in which some of the internal positioning members are adjusted to selectively limit displacement and contraction of the plate in an intermediate region of the protective body portion. [Figure 10B] FIG. 10B is a top view of a portion of the freeze / thaw containment system of FIG. 10A, but with another type of ribbed pattern and with a sample unit attached to the system. [Figure 11] FIG. 2 is a vertical cutaway view illustrating a frame profile suitable for supporting a fixing element and suitable for the integration of a positioning member formed as a slider inwardly movable relative to a stationary frame part. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0061] In the various drawings, the same reference symbols are used to designate identical or similar components.

[0062] In the different figures, the vertical, longitudinal and transverse directions are based on the freeze / thaw storage system being stored horizontally in shelves. The direction perpendicular to the longitudinal direction is the transverse direction. One direction through the height of the freeze / thaw storage system 1 is the vertical direction, which is reflected inter alia by the direction Z in FIG. 4.

[0063] In an embodiment of the present invention, the freeze / thaw containment system 1 can be as illustrated in Figures 4, 6A and 10A and includes a protective body portion (12, 112, 212) covering both sides of a flexible pouch 2 for a biopharmaceutical material (hereinafter referred to as biopharmaceutical composition Q).

[0064] 1-2 or 3, the protective body part 12 or 112 includes two plates 12A, 12B for protecting the flexible pouch 2. The two plates 12A and 12B can be made separately. The protective body part 12 or 112 typically includes ribs on each plate 12A, 12B, while the protective body part shown in FIG. 4 includes at least one outer surface S without ribs.

[0065] The protective body part 12, 112, 212 is obtained by fastening the two plates 12A, 12B in a peripheral part surrounding the covering part 8 belonging to the protective body part 12. For example, the protective body part 12, 112, 212 can be assembled by fixing the peripheral parts of the plates 12A and 12B together when the covering parts clamp the empty pouch 2. In this regard, a mounting device or mounting system 18 is provided for fastening the two plates 12A, 12B. In the assembled state of the two plates 12A, 12B, the protective body part 12, 112, 212 includes a peripheral margin 80. The peripheral margin 80 is obtained by fastening the respective marginal parts 8a, 8b of the plates. Each plate annular margin can be composed of four outer band areas of the plates 12A and 12B. As illustrated in Fig. 1 and Fig. 4, the flexible pouch 2 can be directly protected by the two plates 12A, 12B of the protective body part 12. The mounting system 18 can be included in the plates and / or in a positioning member PM supported by the protective body part 12 at the peripheral margin 80. In some options, the positioning member PM can form a guide part for receiving one or more body cross members. With reference to Fig. 6B, a hole 18o can be provided in the positioning member PM for introducing a rod-like cross member cooperating with a lock part, a nut or a bolt. Of course, a slot can be provided in the protective body part 12, 112 or 212 for the body cross member to cross the peripheral margin 80 in multiple places.

[0066] In another option, as illustrated inter alia in Fig. 11, the positioning member PM can simply clamp the peripheral margin 80, possibly with an interlocking effect due to embossments B12, B12' (see Fig. 1) provided in the peripheral margin 80. Typically, the positioning member PM (here with a non-continuous distribution) selectively clamps the plate margin parts at the peripheral margin 80, as illustrated diagrammatically in Fig. 3, while being in a state in which they cannot be disassembled when they are introduced into the frame 15 (here, into any elongated cavity CP of the frame 15, as illustrated in Fig. 11), typically inside the profiles 91, 92, 93, 94. Thus, there is no need for any additional insert piece IP, and the margin parts 8a, 8b can be provided with embossments or boss parts B12, B12' for engagement with the corresponding relief (cavity CF1) of the positioning member PM.

[0067] 2-3, the peripheral margin 80 may extend annularly in the protective body reference plane P, the peripheral margin 80 being provided with at least one opening 80a capable of receiving at least one port 24 of the flexible pouch 2. Two forward ports 24 may be provided, for example, one port forming an inlet portion for the flexible pouch 2 and the other port forming an outlet portion for the flexible pouch 2.

[0068] The protective body part 12, 112, 212 can extend planarly along a protective body part reference plane P in the unfilled state of the pouch 2.

[0069] The system 1 is suitable for storing and freezing / thawing a biopharmaceutical composition Q (see FIG. 7B). With reference to FIGS. 4, 6A and 10A, such a system 1 is here horizontal, using a horizontal frame. However, the system can also be vertical in a variant, such that the pouches 2 can be stored vertically in the cavities of a vertical frame-like holder (see for example the pouches described in WO03037082, which are received vertically by the use of a rigid slotted frame). To form a compact holder capable of accommodating the respective marginal parts of the storage unit 10, the use of a rectangular frame 15 (provided with an inwardly opening slot or cavity CP) can be of interest.

[0070] The flexible pouch 2 is typically a 2D type pouch, which is bounded by two longitudinal sides LS1, LS2 and has a substantially rectangular shape without predetermined folds on its two main outer faces, as illustrated in FIG. 1 (empty pouch). The pouch 2 therefore extends substantially planarly in the unfilled state. The pouch 2 may have two main walls W1, W2. These walls W1, W2 are directly welded to each other at a weld or peripheral seal J and may define an internal volume for storing a biopharmaceutical fluid Q. More generally, the flexible pouch 2 may be of any suitable material for storing a biopharmaceutical composition Q, forming a freezer bag, which may be of large volume (typically greater than or equal to 5 L). More generally, the flexible pouch 2 is of a first volume and the pouch 2 is expandable to have an increased thickness in an intermediate region away from at least four pouch corners, such thickness increasing with the level of filling of the pouch 2.

[0071] With reference to FIG. 1, the flexible pouch 2 extends in a main plane XY, which here is a horizontal plane. The pouch 2 has a longitudinal axis A parallel to its long sides, which here are the two longitudinal sides LS1, LS2 in the non-limiting illustrated embodiment. The flexible pouch 2 is clamped by the plates 12A, 12B and cannot be removed without first removing at least one of the two plates 12A, 12B. The plates 12A, 12B are typically rigidly attached to each other without being fixed to the pouch 2. A holding and sustaining assembly HR can be provided in addition to the mounting system 18 to hold the unit consisting of the protective body part 12 and the mounting system 18.

[0072] The storage unit 10 provides efficient protection during freezing, storing and thawing operations with the biopharmaceutical composition Q stored in the receiving portion 2r of the flexible pouch 2. The covering portion 8 of the protective body part 12 is less flexible than the receiving portion 2r of the flexible pouch 2 due to the difference in material (it is more rigid with respect to the two pieces forming the plates 12A, 12B). When installed and maintained in a horizontal orientation by the holding and sustaining assembly HR, the two plates 12A, 12B form the lower and upper surfaces of the protective body part 12, 112, 212, respectively.

[0073] Referring to FIG. 2, at least one of the lower and upper surfaces is a storage unit outer surface, which is optionally provided with fastening members 146', 147', 148' to allow fastening of bag 2', either directly or indirectly.

[0074] 6A, the storage unit 10, now independent of the holding and sustaining assembly HR, is capable of supporting a bag 2'. This bag 2' is capable of storing a composition representative of a biopharmaceutical composition Q. The volume of the bag 2' is a second volume that is lower than the first volume, preferably an order of magnitude lower (i.e., at most one tenth lower).

[0075] In another option, as shown in FIG. 10B, the bag 2' is inside a casing 130 and is supported by a frame 15 or any suitable retention and sustainment assembly HR such that the bag 2' typically extends parallel to and above the protective body portion 12.

[0076] The bag 2' and / or the casing 130 storing the bag 2' may be provided with fastening elements 132, 133, 134 cooperating with the fastening members 146, 147, 148 or 146', 147', 148' to allow the bag 2' to be fastened (directly or indirectly) to the protective body part 12, 112, 212 and / or to a mounting set provided in the frame 15. To allow the casing 130 to be secured to extend along one of the outer surfaces S, S' of the storage unit 10, the fastening elements 132, 133, 134 may be distributed around the storage part 200 of the bag 2', here around the casing 130, which may include a compartment for accommodating the storage part 200. The storage part 200 of the bag 2' is the part of the bag 2' that defines the second volume.

[0077] 5A and 5B now show two variants of a casing 130 with different arrangements of the fastening elements 132, 133, 134. In FIG.

[0078] In the option of FIG. 5A, the fastening elements 132, 133, 134 essentially extend along the same direction, which is transverse or perpendicular to the length extension of the protective body part 12 in the assembled state, as shown in particular in FIG. 10B.

[0079] Each pouch 2 can be filled with a solution (fluid composition Q) that is to be frozen and held with slight compression between the two plates 12A, 12B that serve as heat exchange surfaces. For this purpose, the plates 12A, 12B completely cover the pouch 2 at least in the fluid receiving portion 2r, i.e. in the area that defines the internal volume of the pouch 2 (i.e. typically all the walls W1, W2 except for the possible annular seal J and optional outer extensions). In the illustrated embodiment, the pouch 2 is completely covered by a protective body portion 12, 112, 212 formed by the two plates 12A, 12B. During the freeze / thaw operation, the plates 12A, 12B are cooled / heated, for example, by circulating a heat transfer fluid from an external programmable refrigeration unit. The slight compression (containment effect) provides improved contact and heat transfer, resulting in a frozen pouch having the general shape of a pillow (see especially Figs. 4 and 6A).

[0080] The pouch 2 (sandwiched between the plates 12A, 12B) can be mounted in a frame 15, here a rigid frame that can withstand temperatures below 0° C., to avoid damage to the inner material during handling and transport. Referring to FIG. 4 and FIG. 6A, the frame 15 can be part of a support structure, where the frame 15 is a modular part of a device or shelf that can be positioned in a freezer. Rollers (not shown) can be provided to facilitate transport. The frame 15 is typically a rectangular protective frame that leaves the outer surfaces S, S′ of the protective body 12 exposed but forms four protective sides around the storage unit 10. The frame 15 can be included in a retaining and sustaining assembly HR, which also includes a positioning member PM that is engaged with the peripheral margin 80 of the protective body 12, 112, or 212, as illustrated in FIG. 8, among others. The assembly may include multiple feet, possibly of tubular shape, suitable for stacking.

[0081] More generally, the pouch 2, the protective body part 12, the sample unit SU (including the bag 2′ and the casing 130), and the retaining and sustaining assembly HR may define a freeze / thaw containment system 1 in which the outer surfaces S, S′ (here corresponding to the lower surface S′ of the lower plate 12A and the upper surface S of the upper plate 12B) remain exposed (uncovered), while the flexible pouch 2 is located inside the storage unit 10 and is covered by the two plates 12A, 12B. The protective body part 12 has a peripheral margin 80 that is engaged in the gap of the retaining and sustaining assembly HR. The storage unit 10 is suitable for use in freezing, storing, and thawing a biopharmaceutical fluid / composition Q contained within a flexible pouch 2, with the fluid typically being introduced after assembling the storage unit 10 with the flexible pouch 2 (which is typically a disposable pouch) housed within a protective body portion 12, and after the storage unit 10 is mounted within a frame 15.

[0082] In Figures 6A and 7B it can be seen that the pouch 2 is accommodated in the storage unit 10 inside a protective body part that is sustained by a frame profile or similar protective part. This storage unit 10 comprises a protective body part 12 and a positioning member PM that forms an interface for mounting the storage unit 10 in a protective shell or assembly HR that comprises two or four protective parts, which can be elongated profiles 91, 92, 93, 94. The use of four rigid profiles is of interest to form a rectangular frame 15. Optionally, the pouch 2 can be of the Flexboy® type (possibly with a volume of 50 L or more) and is therefore a sterile single-use disposable container that is adapted to be surrounded by a frame 15 that is obtained after assembling the profiles 91, 92, 93, 94 or similar holding elements.

[0083] In some options, the holding and sustaining assembly HR can have fewer than four members so as not to form a rectangular frame. For example, only three members can be sufficient, with a transverse member interconnecting two longitudinal covering parts 31, 32 parallel to the longitudinal axis A of the pouch 2. FIG. 3 only shows two covering parts 31, 32, which can be integral with the foot or associated with a transverse structural member. In some options, 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 pouch stores more than 50 L (e.g., about 75 L, or at least 100 L). FIGS. 4, 10A, and 11 show exemplary parallel covering parts 31, 32, which include two single-piece profiles 93, 94. Each single-piece profile 93, 94 can be hollow and typically defines an elongated cavity CP for the insertion of a positioning member that allows the storage unit 10 and the reference plane P to be positioned vertically relative to the feet 115 connected to the covering parts 31, 32. The feet 115 allow the reference plane P to be shifted upwards compared to the ground level. This is of interest in order to allow a vertical expansion of the covering part 8 belonging to the protective body part 12, which here extends substantially horizontally.

[0084] 3 and 7A-7B, the pouch 2 can have a form or shape that is initially planar in the empty state. The pouch 2 is flexible so as to be expandable and can be made from a pair of flexible sheets (forming respective walls W1, W2) having a rectangular or other planar form, joined together at four peripheral edges, providing a containment volume (internal volume for composition Q) between sheets 21 and 22, which are spaced apart by a predetermined distance in the filled state. One or more openings or ports 24 can be provided (e.g., formed as closable tubes between opposing parts of said peripheral edges of the sheets) to allow the pouch 2 to be filled or emptied.

[0085] Pouch 2 is also designed to provide a high surface area / volume ratio at a low thickness or spacing. As a non-limiting example, pouch 2 can have rectangular dimensions of about 600 mm by about 1300 mm or 1400 mm, and / or a holding volume between about 10 liters and about 120 or 200 liters (preferably between 50 liters and 120 liters), and / or a spacing or pouch thickness (height along the Z direction) between about 8 mm or 10 mm and about 25 mm or 30 mm.

[0086] Each pouch 2 may be made from any suitable biologically compatible material, which preferably promotes heat transfer between the inside and outside of the pouch 2. It is preferred that the material will have a lower glass transition temperature than that of the biopharmaceutical material to reduce or avoid damage to the pouch 2 during cryopreservation due to expansion of the biopharmaceutical material. As a non-limiting example, each pouch 2 may be made from a multi-layer composite material made only from a thermoplastic material (e.g., including at least a layer of polyethylene (PE)).

[0087] The protective body portion 12 and the flexible pouch 2 include a longitudinal direction X and a transverse direction Y. The protective body portion 12 and the flexible pouch 2 include respective longitudinal sides and transverse sides. The longitudinal axis X1 of the protective body portion 12 may be located in a central vertical plane separating the two symmetrical halves of each plate 12A, 12B of the protective body portion.

[0088] The pouch 2 optionally comprises one or more tubes T joined (at a transverse side) to a front end extending transversely to the longitudinal sides LS1, LS2. More generally, the pouch 2 may comprise one hose / tube or any suitable number of tubes connected to the periphery of the useful part of the pouch 2. This useful part is here formed by two main walls W1, W2.

[0089] Protective body 1 and 3-4, the protective body part 12 or 112 includes or consists of two plates 12A, 12B for protecting the flexible pouch 2. The plates 12A, 12B are here completely separate without any hinged or connecting parts. Typically, the plates 12A, 12B are two separable pieces. These pieces are relatively rigid, for example, sufficiently rigid so that they cannot form a fold line with a bending angle of more than 45°. Thus, the plates 12A, 12B are configured to remain relatively flat. The protective body portion 12, 112, 212 includes a longitudinal axis X1 and has four sides 120a, 120b, 120c, 120d, including two longitudinal sides 120c, 120d extending parallel to the longitudinal axis X1 and two other sides including a first end side 120a and a second end side 120b that are respectively perpendicular to the longitudinal axis X1.

[0090] 1-3, in each plate 12A, 12B, a first group of ribs is provided with ribs R1, R2, R2', 800 that are located close to the peripheral margin 80. An optional second group of ribs can be provided with ribs R3, R4, 83, 84, 85, 86 that are located at a greater distance from the peripheral margin 80. Such ribs of the second group can surround one or two panel parts PP, PP1, PP2 on the respective outer surface S, S' of the protective body part 12, 112, which typically form a rectangular panel.

[0091] In some variants, the number of ribs can be reduced or ribs can be eliminated. When elongated ribs are provided, they are preferably wide enough to form grooves G1, G2 with a rounded profile (when viewed in cross section). Each elongated groove can have an internal width at least equal to 10 mm (typically more than or equal to 15 mm or 20 mm). Due to such grooves, a wavy profile can be locally obtained.

[0092] In the illustrated embodiment, the protective body 12, 112, 212 preferably has a mounting device / system 18 for fastening the two plates 12A, 12B such that in the assembled state of the two plates, the protective body 12, 112 includes a peripheral margin 80 extending annularly in the protective body reference plane P, as illustrated in Figures 3 and 4. In some options, the peripheral margin 80 extending into the internal gap bounded by the frame 15 is typically a margin without ribs. In a variant, one or more ribs R1 adjacent to the margin parts for the mutual attachment of the plates 12A, 12B can extend into such a gap.

[0093] The protective body portion may be provided with a first end side 120a and a second end side 120b: the first end side 120a is constituted by the ends E1 of the two plates 12A, 12B in the assembled state of the protective body part 12, 112, 212; the second end side 120b is constituted, in the assembled state of the protective body part 12, 112, by the ends E2 of the two plates. One or more ports 24 may project axially outward from the second end side 120b, such that a portion of the pouch front edge is now accessible.

[0094] In the empty state of the pouch 2, the two plates 12A, 12B respectively form a first surface S' and a second surface S of the protective body part 12, 112 covering the pouch 2. When having a substantially horizontal configuration, the first surface is the lower surface and the second surface is the upper surface. A fastening member 146', 147', 148' may be provided on one of these surfaces S, S' near an end side selected from the first end side 120a and the second end side 120b. The embodiment of Figures 2 and 6A illustrates a scheme with small separate areas formed as male parts or embossments for fixing the sample unit SU in a corresponding female part, hollow or aperture 136, as the case may be. Although the fastening members 146', 147', 148' are here all provided on the same piece forming one of the two plates of the protective body part 12, at least one of the fastening members can also be included in the holding and sustaining assembly HR, i.e. in the area extending around the pouch 2 and the covering part 8. For example, the sample unit SU can have several arms or tabs extending from the casing 130 housing the bag 2', at least one of the arms or tabs being a fastening element 132 attached to a transverse profile 91 or similar rigid part contained in the frame 15 of the assembly HR.

[0095] In the embodiment of Fig. 4 and Fig. 10A-B, the sample unit SU is not supported by any part of the protective body part 12, 112. In contrast, the arms or tabs of the sample unit SU extend from the casing 130 to join the mounting set including the frame 15, each of the arms or tabs forming a respective fastening element 132, 133, 134 joining such mounting set, typically at a joint located above and around the protective body part 12, 112. At least one of the lower surface S' and the upper surface S can be a surface having a plurality of ribs, the plurality of ribs being distributed on two opposite parts of the surface, which are longitudinally opposite parts. Preferably, the plurality of ribs includes a first transverse rib portion 4 proximal to the first end side 120a and a second transverse rib portion 6 proximal to the second end side 120b.

[0096] Such transverse ribs provide an accordion effect due to the width of the corresponding grooves G1, G2 formed by the ribs and / or the height of the ribs (depth of the grooves G1, G2), which promotes local expansion of the plates 12A, 12B despite the planar structure of the peripheral margin 80 forming the protective reference plane P. Typically, in the corner region CR, the first and second transverse rib portions 4, 6 have heights that decrease as the spacing from the corner apex of the plates having such rib portions 4, 6 decreases.

[0097] Thus, excessive expansion that may generate undesired folding (along the diagonal) can be limited or prevented when having a height reduction for the corner rib portion extending into the corner region CR. In other words, the accordion effect can be practically reduced in the four corner regions CR of each plate 12A, 12B. More generally, it is useful to structure the plates 12A, 12B with the first and second transverse rib portions 4, 6 to promote spreading of fluid toward the margin 80 and toward the corners of the protective body portion 12, 112 when filling a flexible pouch 2 sandwiched between the plates 12A, 12B.

[0098] This is of interest in order to have or improve abdominal retention effect. Indeed, the more fluid can be distributed towards the four corners, the less the pouch 2 bulges in the middle area. The protective body part 12, 112 can typically move in the gap of the retention and retention assembly HR, as described in more detail below. Moreover, the structuring effect of the ribs can prevent the fold lines from forming substantially along the diagonals DL1, DL2 when the thickness / expansion difference between the middle area including the center C of the protective body part and the covering part edge is too significant. In some options, the corner ribs are not present.

[0099] Some detailed embodiments of the protective body part 12 or 112 provided with a ribbed pattern will be described hereinafter.

[0100] Plates 12A, 12B as shown in Fig. 1, 2, 4 and 7 correspond to a first embodiment of the protective body 12, in which several ribs are provided. On the outer surface of each of the plates, ribs are provided so that the inner surface is provided with grooves. Some grooves G1, G2, such as those shown in Fig. 1, include transverse groove portions that extend perpendicularly to the longitudinal axis X1 and near the opposite end sides 120a, 120b of the protective body. An annular rib R1 (projecting upwards at the outer surface S or S') can be provided to define the groove G1, which is of annular shape on the plate inner surface. Two separate ribs R2, R2' projecting upwards on the outer surface S or S' may be provided so as to define one or two grooves G2, respectively, of annular shape on the plate inner surface.

[0101] Thanks to the ribs R1 and R2, R2', a pair of transverse rib portions 4, 6 (here parallel to the Y axis (perpendicular to the longitudinal axis X1)) can be arranged near each end side 120a, 120b. In other words, the ribs form a first transverse rib portion 4 proximal to the first end side 120a and a second transverse rib portion 6 proximal to the second end side 120b.

[0102] 1-2, it can be seen that each plate 12A, 12B can be rectangular with four corner regions CR, two imaginary diagonals DL1, DL2 (plate diagonals) intersecting a pair of corner vertices of the four plate corners, respectively. More precisely, each of the two imaginary diagonals DL1, DL2 intersects: - a first series of corner ribs C1, C2 located proximal to the first end side 120a and projecting outwardly along a direction perpendicular to the protective body reference plane P; a second series of corner ribs C1', C2' located proximal to the second end side 120b and projecting outwardly along a direction perpendicular to the protective body reference plane P; Each of the corner ribs C1, C2, C1', C2' is curved and connects two rib portions perpendicular to each other, so that here, the annular rib R1 may include two pairs of corner ribs C1, C1', respectively.

[0103] While the embodiment of Figures 1-2 shows a ribbed pattern (where the ribs can be thought of as peripheral ribs arranged around the central panel portion PP of plates 12A, 12B), Figures 3 and 6A show that ribs can be provided in the intermediate region MR, possibly extending transversely to separate two panels PP1, PP2 of the same plate.

[0104] Although the same ribbed pattern is provided in the two complementary plates 12A, 12B in the embodiment of Figures 1-3 and 6A, in variants some differences may be provided. Optionally, one or two of the plates may be deprived of ribs.

[0105] The plates 12A, 12B form reinforcing layers when they overlap (and preferably completely cover) the main walls W1, W2, respectively. The thickness of each plate 12A, 12B before thermoforming is about 1.27 mm and / or can be less than 2 mm, and the plastic material of the plates has a modulus of 1.10 g / cm 3 Preferably, the density is greater than 1.15 g / cm 3 Density above 1.5 g / cm 3 or 1.6 g / cm 3The plate material may have a tensile strength at break, typically between 45 MPa and 75 MPa, for example in the range of 50-60 MPa, typically in the range of 52-59 MPa (standard test ASTM D638).

[0106] Although the illustrated embodiment shows the protective body part 12 completely covering the two main walls W1, W2 by the covering portion 8, other sizes can also be used for the covering portion 8. For example, the protective body part 12 can cover only a transverse band portion of each wall W1, W2 at a predetermined distance from one of the two pouch opposite edges. Moreover, one or more complementary protective body parts can be used to cover at least one of the end parts of the walls W1, W2.

[0107] Detailed embodiments of the mounting system for mounting the plates together The protective body part 12 may have a covering portion 8 for covering the pouch 2 and two opposite margin portions 8a, 8b at two longitudinal sides 120c, 120d of the protective body part 12. In the unfilled state of the pouch 2, the protective body part 12 extends flat along a protective body part plane P and remains flat. The plates 12A, 12B remain attached at several places of the peripheral margin 80 during handling of the system 1 thanks to the attachment system 18.

[0108] The protective body portion 12 can be transparent, for example the pouch 2 is also transparent. The plates 12A, 12B can have a general curvature but cannot bend easily (flexibility is substantially as low as PET). The peripheral margin 80 can form an annular attachment area where no bending is allowed.

[0109] 2, the protective body part 12 is also provided with a mounting system 18 for fixing the two plates 12A, 12B to one another around the covering part 8. The plates 12A, 12B can be removably fixed to one another by the mounting system 18, which is distributed in a peripheral margin 80.

[0110] Optionally, the attachment system 18 can include multiple snap buttons. One of the two plates 12A, 12B includes a first element of a snap button, and the other plate includes a second, complementary element of a snap button. With reference to FIG. 2, the second element 18b (possibly a male element) engages with the first element 18a (possibly a female element) in a direction parallel to the vertical axis Z.

[0111] Alternatively, the mounting system 18 is a non-removable system, which means that once the two plates 12A, 12B are fixed to each other, it is no longer possible to detach the two plates 12A, 12B from each other.

[0112] In the non-limiting embodiment of FIGS. 1-2, the protective body part 12 is - snap buttons 18a, 18b on the transverse sides 120a, 120b and on the two marginal parts 8a, 8b; and / or - an aperture 102 for receiving an insert piece IP or similar anchoring member not included in the plates 12A, 12B (see Figures 6B and 7A) It is possible to include:

[0113] In the option of using snap buttons or similar fastening parts included in the plates 12A, 12B, such fastening parts can be symmetrically arranged on the transverse ends of the two plates 12A, 12B. Alternatively, the protective body part 12 can include more snap buttons on the front side 120a than on the rear side 120b.

[0114] In some embodiments, the fastening parts used for the mutual attachment of the plates 12A, 12B can also form protruding reliefs or hollows involved for receiving / inserting the positioning members PM. For example, at least two of the embossments B12, B12' shown in FIG. 1 can cooperate with an elongated positioning member PM (here formed as a parallelepiped piece) as shown in FIG. 11 by forming a receiving portion. The insert effect is obtained by pressing the insert surface of the respective positioning member PM towards a complementary receiving portion provided in the peripheral margin 80. Each plate 12A, 12B can receive such a positioning member PM, typically with a regular distribution around the covering portion 8 of the protective body part 12, as shown for example in FIG. 3 or FIG. 8 (non-limiting examples).

[0115] More generally, the attachment system 18 can include any suitable mechanical fasteners typically disposed between the covering portion 8 and the longitudinal sides 121, 122. Typically, the two opposing marginal portions 8a, 8b can be considered as part of a fastening assembly provided to prevent any shifting movement of the position between the two plates 12A, 12B when the two plates 12A, 12B are fastened to each other at the at least two marginal portions 8a, 8b.

[0116] As can be seen in Figures 2-4, 6A-6B, and 7A-7B, when the two plates 12A, 12B are fixed to each other, they sandwich the flexible pouch 2. The planar plate 12A (which forms the lower surface S' of the protective body part 12) presses the lower surface of the flexible pouch 2 against the vertical axis Z. Similarly, the planar plate 12B (which forms the upper surface S of the protective body part 12) presses the upper surface of the flexible pouch 2 against the vertical axis Z. The two plates 12A, 12B can have planar dimensions substantially identical to those of the flexible pouch 2.

[0117] Retention and Sustaining Assembly 2, 3, 4 and 10A, the holding and sustaining assembly HR comprises a frame 15 and, optionally, a positioning member PM, which either cooperates with or is part of the mounting system 18. The positioning member PM (here covering or included in the mounting system 18) can move with respect to the frame 15, which acts as a stationary part of the holding and sustaining assembly HR. In some embodiments, the two longitudinal covering parts 31, 32 comprise a profile and can also be considered as belonging to the holding and sustaining assembly HR. The positioning member PM can be introduced into the profile of the frame 15 or can be attached to the same covering parts 31, 32 before assembling the assembly HR (typically before assembling the frame 15).

[0118] The two covering parts (such as those shown in FIG. 3) are arranged to maintain the two longitudinal marginal portions 8a, 8b of the peripheral margin 80 while allowing the two plates 12A, 12B to move, expand and contract in a transverse direction belonging to the protective body reference plane P. As shown in FIG. 4A and FIG. 11, the two longitudinal covering parts 31, 32 can include two profiles 93, 94 that respectively define the boundaries of the internal cavities CP. In a non-limiting embodiment, the gap can be the internal cavity CP of each of such covering parts. Each of the two longitudinal covering parts 31, 32 can include a substantially C-shaped or U-shaped profile to define one of the internal cavities CP.

[0119] 2, 6A and 10B-11, it can be seen that the pouch 2 is sandwiched between the plates 12A and 12B, but without interfering with the hose or tube T, respectively, provided with an end connector 17. The protective body portion 12, 112, 212 can be assembled first, and then the two protective parts 31, 32 are assembled to complete or cover the mounting device 18.

[0120] Typically, the holding and sustaining assembly HR comprises a frame 15 (here of rectangular shape) provided with four sides. The longitudinal covering parts 31, 32 may be protected in profiles 93, 94 forming the two longitudinal sides of the frame 15. Other covering parts provided along the transverse sides of the protective body part 12, 112, 212 may also be included in the mounting system 18. Optionally, such other covering parts may be housed / protected in the profiles 91, 92 forming the two transverse sides of the frame 15.

[0121] More generally, several profiles can form all or part of the frame side. At least four rigid profiles 91, 92, 93, 94, preferably 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 slides for respectively receiving at least three of the positioning members PM separated and distributed along the length of the frame 15. Optionally, the two other profiles 91, 92 can also form slides (here transverse slides) for receiving the transverse sides 120a, 120b of the protective body parts 12, 112, 212. Similar positioning members PM can be slidably mounted in the rail-like profiles 91, 92.

[0122] The holding and sustaining assembly HR can maintain the protective body part horizontally or vertically, the frame 15 is also of interest for forming a peripheral protection around the protective body part 12, 112, 212. The peripheral frame 15 houses an internal positioning member PM having a certain size along the Z direction, which is larger than the corresponding size (along the same direction) of the opening in the open side of the profile 91, 92, 93, 94. Four similarly constructed profiles 91, 92, 93, 94 are provided here to house a positioning member PM on each of the four sides, but variants with one or two sides without such a positioning member PM can also be provided. Moreover, variants with another type of covering parts 31, 32 can be provided either with the ability to have shrinkage management of some sides of the protective body part 12, 112, 212 or without the possibility of having such shrinkage management (for example, if the volume of the pouch 2 is relatively low).

[0123] The structure shown in FIG. 4 is of interest for relatively large volume pouches 2, which are capable of having significant bulge B without shrinkage control at the peripheral margins 80.

[0124] The holding and sustaining assembly HR can be assembled after mounting the positioning member PM to the peripheral margin 80. As illustrated in Fig. 10A-B, corner sections 15c can be used between adjacent vertical profiles. At least two corner sections 15c can be fastened to the transverse profile 91 (which here is the rear profile) before or after installing the longer profiles 93, 94. The positioning member PM can be arranged on the outside of the corner sections 15c. One or two corner sections 15c and at least three profiles 91, 93, 94 of the frame 15 can be provided to form a mounting set that is engaged to support the protective body part 2. The mounting set further serves as a receiving device for the attachment of the sample unit SU.

[0125] Referring to FIGS. 10A and 10B, fastening members 146, 147, and 148 are - on the two corner sections 15c; as well as - on two supporting accessories which are directly engaged in the longitudinal profiles 93, 94 or similar covering parts of the holding and sustaining assembly HR It can be distributed.

[0126] Here, three separate support members belonging to the holding and sustaining assembly HR are capable of forming a rigid peripheral part that combines a first function of mounting / holding the storage unit 10 along a typically horizontal plane with a second function of supporting or forming several fastening members 146, 147, 148 each extending above the protective body part 12 for interlocking with complementary fastening elements 132, 133, 134 extending around the casing 130 of the sample unit SU or similar storage part.

[0127] The rigid peripheral part can be a frame 15 as shown in Fig. 6A or Fig. 10A. When the four corner sections 15c interconnect the frame profiles 91, 92, 93, 94, the peripheral margin 80 can have only one open side located between two corner sections, which is laterally covered by the profile 92 provided with an opening. On the frame side opposite such a profile opening for the port 24, the two corner sections 15c can directly define two fastening members 146, as shown in Fig. 10A-B, for fastening of the casing.

[0128] Of course, the frame 15 can be formed in various ways using any suitable hard covering parts capable of protecting the areas / locations of the storage unit 10 and the areas / locations of the sample unit SU. Preferably, the frame 15 surrounds the casing 130 of the sample unit SU and is capable of maintaining the sample unit SU in a position close to the plate of the protective body part 12, 112, 212 with or without contact with the protective body part.

[0129] Tubing Holder 6A, two hoses or tubes T are typically connected to the front edge of the flexible pouch 2. The rear edge of the flexible pouch 2 can extend substantially parallel to the front edge at its opposite longitudinal end. Each tube T can be bent and have a length that exceeds the length of the longitudinal sides LS1, LS2 of the pouch 2, although any size hose / tube can be used. Each tube T can be maintained substantially parallel to the protective body reference plane P by attachment to a tubing holder provided in or attached to the frame 15 of the assembly HR.

[0130] Each hose / tube T is provided with a connector 17 for fluid connection (typically to another biopharmaceutical device). The connector 17 thus allows for fluid connection of the flexible pouch 2 to another element (e.g. a tank). In a storage position of the tubes by use of the fastening means MF1, MF2, the respective connector 17 can be positioned between the longitudinal rear side 120b of the protective body part 12 and the middle region MR.

[0131] 4, one or more of the elongated profiles (here profile 94) may be provided with one or more fastening means MF1, MF2 for supporting at least one tube T connected to port 24 or contained within pouch 2 as an extension defining port 24. The tubing holders (including fastening means MF1, MF2) may be distributed in at least two spaced apart locations along a side of frame 15, in the peripheral area of ​​system 1.

[0132] The frame 15 is provided with clamping members and / or grooves G9 (see FIG. 11) for holding one or two hoses / tubes T (see FIG. 10B) connected to the pouch 2 via the port 24, thus making it possible to form a tubing holder. Such a tubing holder has holding parts distributed on at least two or three profiles 92, 93, 94 and optionally on one or two corner sections 15c. Here, one or two profiles arranged perpendicularly to the front profile 92 include, in a preferred option, part of such holding means to hold the hose T above the protective body part 12. Depending on the ease of access to the top or bottom of the protective body part, the tubing holder can also extend below the protective body part 12 in some variants using grooves G9 arranged below the protective reference plane P.

[0133] It is understood that the tubing holder is located completely outside the cavity CP in order not to interfere with the peripheral margin 80 and therefore with the freedom of movement of some of the positioning members PM. When the groove G9 is provided in the longer profile 92, 94, the groove G9 can be substantially as long as the flexible pouch 2 and / or can be substantially as long as the space delimited between the opposing transverse profiles 91, 92. This allows flexibility in using the groove G9 to position the fixing means MF1 provided with an anchor fixing piece.

[0134] In a first option, the fixing means MF1 of the tubing holder comprises one or more anchoring pieces with an anchoring relief 160 having a complementary shape with respect to the receiving groove G9 of one of the longer profiles 93, 94, as is evident in FIG. 11. Each anchoring piece may also be provided with an abutment end 162 in contact with a surface (here a substantially vertical surface) of the inner section 15a. The anchoring pieces may extend upwards from a joint part joining the anchoring relief 160 and the abutment end 162, such joint part being optionally a hollow or recessed part, improving the deformation of the anchoring relief that may be clipped into the groove G9. Here, the anchoring pieces are inclined (inwards) with respect to the Z direction. There is no overlap of the sample unit SU with respect to the frames 93, 94, which may be useful for easily positioning the foot 115 or a similar vertical post, allowing the two systems 1 to be superimposed without interference with the mounting / removal operation of the sample unit SU.

[0135] In a variant, the anchoring piece can either be fitted or screwed into a female part contained in the profile 93 or 94, or be provided with a female part end which cooperates with a male part of the profile 93 or 94. This is preferably a removable attachment.

[0136] Typically, the anchor fixing piece may further comprise at its upper end a fastening member 147 for holding the sample unit SU parallel to the frame 15 (and thus, in the embodiment shown, substantially parallel to the reference plane P). Such a single-piece construction of the fixing means MF1 simplifies the mounting step. It may also be of interest for receiving two or more components, especially when it also has a sample unit SU supported by the fixing means MF1 (whose positioning is easily adjustable in length along the profile 93 or 94). Other suitable fixing means may also be used for the removable attachment of the anchor fixing piece to the frame 15, such anchor fixing piece serving as a fastening member to the frame 15.

[0137] In some options, an anchor fixation piece or similar retaining piece may not be used to attach the tube T, but may serve only as a fastener 147 or 148 .

[0138] It can be seen that the sample unit SU is mounted above the two longer profiles 93, 94 at a predetermined distance from the rear corner section 15c, while also being attached to one or more fastening members 146 located at the rear end of the frame 15. In some options, such additional fastening members may be formed near the protective body part rear end (typically outside the peripheral margin 80).

[0139] With reference to the options illustrated in Figures 4C and 6E, the hose / tube T is in the groove G9 (in the part of the groove G9 that is remote from the rear profile 91 and close to the front profile 92), and - In the blocking groove BG of the anchor fixing piece It can be simultaneously accepted and / or guided. This is of interest in order to have a compact arrangement of the entire system 1, the outer periphery of the system being bounded only by a profile (here by the outer section 15b of the frame 15), which effectively acts as protection for the pouch 2 already clamped between the two plates 12A, 12B.

[0140] The fixing means MF1 is easily removable, since a simple rotation of the anchor fixing piece may be sufficient to disengage this piece from the groove G9. There is no need for a tool to remove the hose / tube T from the guide groove G9, because the tube end is already available / outside such groove G9 by being clipped into the blocking groove BG, which is very short compared to the elongated groove G9.

[0141] 6A-6B and 7, the fastening means MF1, MF2 can comprise at least one fastening element 110, which here can be snapped onto the frame 15 by engaging onto an outer part of a rail-like profile of the frame 15. For example, the fastening element 110 is a bracket partially surrounding a receiving profile, which can be one of the longitudinal profiles 93, 94 or another profile 91, 92. Here, the fastening element 110 is a single piece made of plastic material and has an inner surface F110 that can locally match the outer surface F94 of the corresponding profile 94. The fastening element 110 can be engaged on the side opposite to the open side of the profile.

[0142] The fixing element 110 is here C- or U-shaped in cross section and therefore forms a bracket with an almost closed internal face F110. The bracket bounds an internal space or recess for receiving a portion of the profile 94. The two opposing rims 110b project / project towards each other from opposite parallel parts of the internal face F110, narrowing the open side of the bracket, as shown in FIG. 6B. The two opposing rims 110b are continuous rims, which are in contact with the inner side of the receiving profile, such that the fixing element 110 is prevented from moving outwards relative to the receiving profile, which is here the profile 94.

[0143] A protruding pin 110a may be provided in this piece (or vice versa in the receiving profile) to form an inwardly protruding indexing member. The fixing element 110 also includes a clamping part 113, which forms a receiving cavity bounded by a concave inner surface 113a. A portion of the tubing outer wall, which may be cylindrical in shape, may be inserted and fitted into this receiving cavity. The portion of the tube T received in one or two cavities of the fixing element 110 may extend completely above the plane XY when the protective body part and the pouch 2 extend horizontally.

[0144] Compared to the recess for accommodating the profile portion, the cavity delimited by the surface 113a can be shifted inwards. The further the flexible tube T is from the periphery of the system 1, the lower the risk of accidental handling and detachment of this hose or tube T, for example during a transport step. However, this tube T now remains easily available to the operator.

[0145] 6B, a pin 110a can extend parallel to the Z direction and protrude from the inner face 110. This pin 110a or a similar indexing member as well as a clamping part 113 or a similar part for holding the tube 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 part 113 for holding the tube T extends from the outer face of the fixing element 110 on the opposite side.

[0146] The pin 110a is received in a recess or aperture in the receiving profile, which recess or aperture opens outwardly. A pair of two opposite recesses 94a, 94b may be provided in the same longitudinal position of the profile 94 (as considered along the X direction), such that whatever the relative position of the tube T with respect to the frame 15, a recess 94a or 94b is always available.

[0147] When engaged in the recess 94a or 94b, the pin 110a prevents the fastening element 110 from sliding (longitudinally) relative to the receiving profile of the frame 15. In variants, other means (e.g. a gripping surface with a small relief) can also be used to prevent the bracket or similar element 110 from slipping or sliding.

[0148] The tubing holder can be an assembly for holding two tubes T so that they are symmetrically arranged with respect to the longitudinal direction X (i.e., the pouch longitudinal axis A). Each symmetric part can hold one hose / tube T.

[0149] 4 and 6A respectively show a solution for horizontal storage, it is understood that the pouches 2 can also be stored vertically or along any suitable direction thanks to the storage unit 10. A sliding structure can be used to allow the protected pouches (in a frozen state) to be carried by an annular frame or similar holding means that can extend vertically for storage purposes.

[0150] Of course, in the option 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 protective body reference plane P, a fixing element 110 as shown in Figures 6A-6B may be used.

[0151] Filling the pouches Several flexible pouches 2 may be filled and protected in a system 1 as illustrated in Figures 4 and 6A. A shell may be formed by several superimposed systems 1. The flexible pouches 2 in these systems 1 may be frozen, thawed, filled or emptied simultaneously when they are stored on such kind of shell device. When the flexible pouches 2 are stored, the biopharmaceutical fluid / composition Q may be frozen or thawed. When the flexible pouches 2 are shipped, in most cases the biopharmaceutical composition Q is thawed, even though the biopharmaceutical fluid may be frozen as well.

[0152] The flexible pouch 2 is allowed to expand during the filling operation, meaning that the perimeter of the two main walls W1, W2 as considered to be in the pouch plane (corresponding to the protective body reference plane P) is reduced due to the inward movement (also known as the retraction stroke) of the different sides. Now, in a horizontal configuration of the system 1 as illustrated in Figure 4 or Figure 6A, the four pouch sides can be displaced inwards due to vertical expansion (along the Z axis).

[0153] 1-3, due to the lower flexibility of the material of the two plates 12A, 12B (optionally provided with outer ribs), the pouch expansion is limited and controlled by the protective body portion 12, 112. The protective body portion 12, 112, 212 is made of a freeze-resistant polyester or copolyester material that is not brittle at about 25° F. or −4° C. This material is, for example, PET or a robust copolyester of the TRITAN™ type.

[0154] In some options, the peripheral margin 80 is regularly covered by a positioning member PM which is simply inserted onto the respective receiving part comprising an element of the mounting system 18. For example, two boss parts B12 projecting along the Z direction and two boss parts B12' projecting in the opposite direction along the Z direction form a group of four boss parts of the same receiving part cooperating with the elongated positioning member PM.

[0155] The mounting device or system 18 includes one or more cross members or such boss portions B12, B12', which are configured to maintain the positioning members PM in the assembled state. In some options, such cross members may include insert pieces IP (FIG. 7A) and associated fastening locks (e.g., mechanical locks such as nuts or bolts). With reference to FIG. 6B, such cross members exert a holding effect through holes 18o that match slots or apertures 102 provided in the plates 12A, 12B.

[0156] The cross member is part of the attachment means, which can be in a locked state, in which it cannot move or slide along the Z direction through the protective body part 12, 112, 212, to prevent vertical separation of the parts UP, LP of the positioning member PM. Optionally, it can also be the case when having boss parts B12, B12' instead of a cross.

[0157] Referring to Fig. 7A, the upper part UP and the lower part LP typically clamp a peripheral margin 80 of the pouch 2 in an area outside the clamping. Fig. 7A illustrates the initial position of the positioning member PM in an empty state of the pouch 2. A gap is provided between each of the parts UP, LP and the inner side or inner section 15a of the corresponding receiving profile to allow for shrinkage.

[0158] With reference to FIG. 7B, it can be seen that the biopharmaceutical composition Q is introduced into the flexible pouch 2 and each of the positioning members PM can possibly be displaced inwards in the final position (in which the positioning members PM abut inwards against the abutment rims BS, BS2 of the frame profile). Each of the parts UP and LP can include a forward protruding portion 7, 7', which in the filled configuration of the pouch 2 engages / extends through the inner side (elongated) opening of the profile. The forward protruding portions 7, 7' of each of these parts UP, LP can have an inclined surface that reaches the pressing surface in contact with the protective body part 2, so as to form an inwardly opening V-shaped cross-section groove GS (distributed on both sides of the body part peripheral margin 80). This groove GS can guide the expansion of the protective body part near the peripheral margin 80 in order to prevent direct contact of the surfaces S, S' against the frame 15 (and therefore any contact against any profile edge / surface). This is of interest to protect the protective body material since the profiles 91, 92, 93, 94 are typically made of harder materials (e.g. steel, metal or hard plastic).

[0159] The two plates 12A, 12B are sufficiently flexible to allow the protective body part 12 to have a localized thickness at or near the central area that is greater than that in the surrounding areas. Thus, when the biopharmaceutical fluid is frozen, the containment area / receiving part 2r or useful part of the flexible pouch 2 (i.e., the inner area relative to the peripheral seal J) can be slightly curved. Thus, the longitudinal (X) dimension of the protective body part 12 is slightly reduced. In this case, the biopharmaceutical fluid is slightly constrained by the two plates 12A, 12B.

[0160] Particular embodiments with a casing for storing sample storage bags 5A-5B, the bag 2' may be optionally provided with hoses 104a, 104b and clamps (here two clamps associated with the two hoses 104a, 104b). Any one of the hoses 104a, 104b may be formed as a closable tube, allowing the bag 2' to be filled or emptied. Each clamp clamps one hose 104a, 104b, respectively, with a straight angle. Also, one or more crimping rings CC are provided, for example, between the clamps and the port 24' of the bag 2'. All these components may be stored in the inner volume V3 of the casing 130 together with the bag 2'.

[0161] The inner volume V3 is delimited by the side wall 131 of the casing 130 and extends between the bottom of the casing and the lid 35. The lid 35 is here a hinged lid, connected to the side wall 131 by a hinge H35, typically a linear hinge. In the closed state, the lid 35 can be locked thanks to a snap button 35c cooperating with an annular frame formed at or adjacent to the annular end of the side wall 131 (i.e. opposite the casing bottom). More generally, the casing 130 can be provided with a closure system, which makes it possible to lock and unlock the folded position of the lid 35, and which preferably extends opposite the hinge H35.

[0162] Typically, the lid 35 cannot be separated from the other walls of the casing due to the hinge connection. The fastening elements 132, 133, 134 can be formed as arms or similar extensions projecting outward from the side wall 131. Thus, the lid 35 can be opened and closed without interference with the fastening elements 132, 133, 134 extending around an annular seat for receiving the annular contact part of the lid 35. The annular contact part surrounds a central covering area of ​​the lid 35, which covers the upper open surface bounded by the side wall 131.

[0163] 4 and 10A-10B, the casing 130 is maintained at a predetermined vertical distance from the storage unit outer surface (i.e., from the protective body portion 12, 112). One or more snap buttons, clips, and / or similar removable fasteners (distributed on different sides of the frame 15) form the anchoring members of the casing fastening assembly.

[0164] With reference to Fig. 10B, it can be seen that one part of the fastening member (here fastening members 147, 148) is formed by an additional piece, which is mounted on the frame 15 and extends upwards from a joining part (for joining to the frame) to an upper fixed end that cooperates with an opening 136 or similar mounting part (see Fig. 5A) provided in the fastening element 132. Another part of the fastening member (here fastening member 146) is formed in the frame 15 and extends to a position not as high as the fastening members 147, 148. This difference in height level is compensated by one or more elongated tabs forming the fastening element 132, each of which is flexible and can be tilted downwards to reach the fastening member 146.

[0165] More generally, the fastening elements 132, 133, 134 may each be made from a more flexible plastic material than the plates 12A, 12B. Respective apertures 136 and 137, 138 may be provided in each of the fastening elements 132, 133, 134 at a distal location with respect to the side wall 131. Such apertures 136 and 137, 138 provided in areas made from a flexible material may readily cooperate with corresponding protrusions provided in the frame 15 and / or on the upper storage unit outer surface.

[0166] In some options, at least two arms or tabs extending in opposite directions from the casing 130 form fastening elements 133, 134 that can be inserted through the profiles 93, 94, for example by sliding in grooves or similar recesses in such profiles 93, 94. Another fastening element 132 can then be fastened to a corresponding fastening member 146' formed on the protective body part 12. Such fastening element 132 can, in some cases, prevent or limit further sliding, thus substantially locking the final mounting position of the sample unit SU. More generally, the casing 130 can be attached by sliding all or part of the fastening elements 132, 133, 134 into the frame 15. The frame 15 may be provided, for example, in two profiles 93, 94, with two longitudinal grooves or similar sliding portions extending parallel above the protective body part 12 and above any elongated opening in the inner section 15a for the passage of the peripheral margin 80.

[0167] In some options, at least two arms or tabs extending in opposite directions from the casing 130 form fastening elements 133, 134 (see FIG. 5A ) that can be inserted through the profiles 93, 94, for example by sliding in grooves or similar recesses of such profiles 93, 94 (the grooves being open at the axial ends as the case may be). Another fastening element 132 can then be fastened to a corresponding fastening member 146′ formed on the protective body part 12 or to a corresponding fastening member 146′ formed on the frame end. Such fastening element 132 can, as the case may be, prevent or limit further sliding and thus substantially lock the final mounting position of the sample unit SU.

[0168] Here, there is an optional part of the bag 2', which is flattened and does not contain any biopharmaceutical fluid. It can form a handle. In the non-limiting embodiment of Fig. 5B and Fig. 6A, the casing 130 is secured to the storage unit outer surface by one or more snap buttons that form the anchoring members (136, 137, 138, 146', 147', 148') of the casing fastening assembly. Here, the rear longitudinal edge of the bag 2' (which is part of the handle) is illustrated as extending outside the casing 130 by protruding between the lid 35 and the casing frame. However, in a preferred option, the bag 2' can be completely contained inside the casing 130.

[0169] In the option of using anchoring projections or other anchoring parts of the protective body part, an optional positive lock can be provided to allow the casing 130 to be attached directly to the outer surface S, which here is the upper surface of the protective body part 12, 112, 212. Similarly, an optional positive lock can also be provided to allow the casing 130 to be attached to the frame 15 by extending as close as possible from the outer surface (but typically with a small spacing gap).

[0170] The casing 130 is here a parallelepiped, but its side wall 131 can be of any prismatic shape, with or without rounded parts.

[0171] Moreover, the side wall portions 131 of the casing 130 may be provided outside the corner regions CR of the protective body portions 12, 112, 212 and / or may be maintained at a distance greater than 120 mm from the peripheral margin 80 (i.e. from the reference plane). In the embodiment of Figure 6A, the casing 130 may be attached to and maintained on a backing region that remains substantially planar during the filling / thawing operations.

[0172] The casing 130, considered as a whole, is of a thickness that is less than the maximum thickness of the flexible pouch 2 in the filled state. This is even more true for the bag 2'. For example, the casing 130 has a thickness (measured along the Z direction) that is less than 50 mm or 60 mm. The thickness of the entire casing can be less than the distance along the Z direction between the reference plane P of the protective body part and the casing 130.

[0173] The fastening elements 132, 133, 134 may only extend from the side wall 131 in a direction away from the middle (away from the centre C) of the protective body part 12. All interlocking or anchoring members 136, 137, 138 provided in the fastening elements 132, 133, 134 are configured to contact the surface S 200 mm or 500 mm beyond the centre C of the protective body part 12 (the centre where the diagonals DL1, DL2 intersect).

[0174] Moreover, it can be seen that the fastening elements 132, 133, 134 extend completely above the protective body portion such that they do not overlap the sides of the frame 15. Thus, the fastening elements can be relatively short straps or tabs such that the maximum extension of the sample unit in width or length cannot exceed the width of the frame 15.

[0175] Details of an Exemplary Embodiment for Controlling Pouch Expansion In the embodiment of FIG. 8, the plate dimensional reduction (when considered in the XY plane) is obtained by the profile of the retraction stroke, and such reduction is adjusted differently depending on the longitudinal position of several positioning members PM that locally prevent or limit such dimensional reduction in order to control the retraction stroke.

[0176] Here, the positioning members PM (which are fixed to the peripheral margin 80 as shown in Figures 7A-7B) are distributed longitudinally and some of them are configured to limit the contraction stroke of the longitudinal sides of the protective body part by a stopping effect resulting from the engagement of the positioning members PM against the inner surfaces of the abutment rim parts BS, BS2.

[0177] All or part of the positioning member PM is a stopper for providing a stroke limit between the stoppers 41, 41', 42 and the abutment surfaces BS, BS2 contained in the frame 15 of the holding and sustaining assembly HR. With reference to Figures 8 and 9A, the stoppers 41, 41' located at or near the mid-section MS of the pouch 2 are involved in creating a belt effect. In some embodiments, such a belt effect separates the two abdomens or bulges B1, B2.

[0178] 8 and 9A-9B, the positioning members can act as stoppers 41 or 41' only in the two middle parts 82 of the protective body part 12. As a result, the pouch 2 covered by the containment protective body part 12, 112 or 212 cannot form a single belly or bulge in the middle, since the stroke is allowed in the area closer to the corner area CR (here, in the end part 81).

[0179] Moreover, the optional ribs prevent the plate outer surface from forming fold lines or hollows that would limit good filling of the biopharmaceutical composition Q in the corner regions. Such ribs, possibly with areas or portions of lower height (e.g., only in the diagonals DL1, DL2, since the guide effect and accordion-like effect are already obtained along the four sides of the rectangular shaped protective body portion 12, 112), may help the protective body portion 12, 112 to expand from the inside without creating hollows or improper fold lines that would be detrimental to filling in the corner regions CR.

[0180] It will be appreciated that at a given level of filling, the pouch corners and protective body corners are allowed to continue to move inwards during the filling operation while the intermediate part 82 is blocked by the stoppers 41, 41'. In the corner regions CR, the retraction stroke is longer than that of the intermediate parts, allowing at least the same liquid volume to be stored as in the absence of belly / bulging persistence.

[0181] Still referring to Fig. 8, the stops 41, 41', 42 can be in place to form a positioning member PM. Here, only the stops 41, 41' positioned away from the end sides 120a, 120b have a relatively closer distance to the central symmetry plane of the protective body part 12 compared to the distance for the stopper 42. In such an option shown in Fig. 8, such stops 41, 41', 42 follow the displacement (contraction) of the peripheral margin 80.

[0182] During the filling operation, the stops 41, 41' provided in the intermediate parts 82 of the longitudinal margin portions 8a, 8b are (first) shifted inwards due to the arrangement of the mounting system 18 and / or due to the asymmetrical arrangement of the positioning members, and since the abutment surfaces SB, SB2 are aligned parallel to the X direction, these stops 41, 41' come into abutment against the abutment surfaces SB, SB2 well before the stops 42 adjacent / facing the corresponding corner regions CR. A belly-lasting effect in the intermediate part of the protective body part 12, 112 is obtained.

[0183] In an option, the ribs R1, R2, R3, R4 are provided in the plates 12A, 12B, possibly provided with corner ribs C1, C2 having a height profile decreasing towards the intersection area with the diagonals DL1, DL2. In such kind of option, the sustaining effect (a bulging effect decreasing in the intermediate area MR close to the center C) is completed by a regular expansion of the area around the panel PP or PP1, PP2, preventing the undesired formation of pronounced fold lines.

[0184] Of course, Fig. 8 is merely an exemplary embodiment for managing the shrinkage of the plates 12A, 12B. More generally, the protective body portion 12 may be fitted to clamp the flexible pouch 2 and may be received / held within the gap of any suitable retaining and sustaining assembly HR, which is rigid and defines the outer perimeter of the system 1. Depending on the level of filling of the pouch 2 clamped by the plates 12A, 12B, the protective body portion 12 may include one or more areas of maximum thickness. To accommodate this thickness variation, the retaining and sustaining assembly HR may be of annular shape.

[0185] One or more bulges / bellies B1, B2 as illustrated in Figures 9A-9B may be formed due to expansion control and early stopping effect in the intermediate parts (e.g., thanks to early blocking stoppers 41 and / or 41'), causing the intermediate section MS to move much less compared to the complementary sections covered by parts of the protective body portion 12 near the first and second end sides 120a, 120b.

[0186] More generally, any configuration may be provided with positioning members that can form stops away from the corner regions CR, such that a higher restraining effect can be obtained in the center of the pouch 2, as illustrated in particular in Figures 9A-9B. This is of interest for managing the freeze / thaw operation of the biopharmaceutical material stored in the pouch 2. It is also of interest for better stacking systems such as those illustrated in Figures 4 and 6A, with higher compactness (less vertical space between two adjacent storage units 10) and thus offering the opportunity to store more pouches 2 in the cryochamber.

[0187] The dashed lines in Fig. 9B show the type of abdomen that is usually obtained when also allowing a large stroke in the respective area of ​​the peripheral margin 80. It is therefore of interest to limit or prevent the displacement of the intermediate parts of the protective body portion 12, 112, 212, so as to limit the accumulated mass (of significant thickness) that may be difficult to unfreeze.

[0188] FIG. 9A shows that the frame 15 or any kind of retaining part of the assembly HR is suitable to allow the protective body part 12, 112, 212 to change its conformation (with a decrease in body width and body length) and thus to reduce: - The width of the pouch 2 (w' < w, where w' is the pouch width in the filled state compared to the pouch width w in the empty state), and, - The length of the pouch 2 (L' < L, where L' is the pouch length in the filled state compared to the pouch length L in the empty state).

[0189] In some variants, the positioning member PM can be positioned in the through slots and maintained in a stationary state by being fixed to or integrated with, for example, the rigid frame 15 or a similar holding and sustaining assembly. The slots in the protective body part can be of a larger size only near the end side parts 120a, 120b, and thus allow for a larger contraction only in the corner region CR, preventing the formation of an overly large bulge near the center C (due to the abdominal effect / sustaining in the intermediate part when the positioning member is an early stopping member).

[0190] The holding and sustaining assembly HR can include at least three positioning members PM distributed at each of the longitudinal side parts 120c, 120d, and typically, one or two central stoppers 41 correspond to the positioning members PM arranged away from the corner region CR.

[0191] In addition to or independently of having such an abdominal sustaining effect, at least one of each system, or of the systems in a stack of systems, can be provided with a sample unit SU that includes a bag 2' in which a small amount representative of the biopharmaceutical composition Q can be stored. In the thawing stage, it may be of interest to have a sample unit SU that provides a small amount of the biopharmaceutical composition Q that has been subjected to the same treatment and the same freezing operation as the composition stored in the large - capacity pouch 2. Being in a small amount, it will heat up faster, thus accelerating the thawing operation for the contents of the sample unit SU.

[0192] The system 1 is well adapted for freezing, storing and thawing biopharmaceutical materials contained in a simple concept flexible pouch 2. The storage unit 10 as described above can be protected by compact peripheral parts without interfering with the filling and expansion of the pouch 2. Such peripheral parts or frame-like structures are of interest for at least one of the following reasons: making the sample unit SU available in the same place as the pouch (typically in the space delimited by the frame 15) and without complex handling; - ensuring that the sample unit SU is efficiently fastened (in some embodiments typically mechanically fastened without apertures / significant protrusions or without creating defects in the protective body) to withstand a large temperature range (without chemical bonds or using adhesive effects), preferably without accessories or bulky intermediate fasteners, - To prepare a biopharmaceutical composition Q with a high level of protection by optimized bulk.

[0193] In an embodiment with an adjustable positioning member PM, the filling of the pouch 2 can be performed with a controlled and limited expansion, such that the expansion is limited in one or more areas where the fluid thickness would reach a maximum in the absence of expansion control. The internal volume or cavity bounded by the main walls W1, W2 is expanded with the prevention of free expansion in the intermediate areas of these walls W1, W2. In particular, the expansion can be limited along one or more belt lines BL joining two intermediate parts 82, as illustrated in FIG. 9A.

[0194] Such a depression along the belt line BL, due to a low or non-existent contraction stroke in the intermediate part 82, typically generates at least one recess in the pouch 2 when filled, and in the stored configuration of the storage unit 10, at least one recess is thus generated in the filled pouch 2 between the two bulges B1, B2. This allows a generally equal distribution of the fluid, since a more uniform thickness distribution is obtained, without reducing the volume of the pouch 2.

[0195] The pouch 2 and protective body portion 12 can be exposed to temperatures of about -70°C or below to freeze the biopharmaceutical fluid / composition Q. The annular shape of the frame 15 of the holding and sustaining assembly HR is of interest to provide a recessed area through which cool air can circulate and flow between the systems 1 (even when the systems 1 are stacked). However, other shapes and structures can also be used to form the holding and sustaining assembly for controlled expansion: - to eliminate or reduce the formation of excessively large protrusions during freezing, Whatever filling level is reached with respect to the pouches clamped by the plates 12A, 12B, this is intended to fix the sample units SU parallel to the substantially flat protective body part 12, 112, 212.

[0196] The present invention has been described in connection with preferred embodiments. However, it is to be understood that these embodiments are merely illustrative and that the present invention is not limited thereto.

[0197] Of course, the pouch 2 of the present invention is in no way limited to a pouch having four sides and / or a pouch that is larger than the width. The pouch 2 can have other shapes provided with two generally parallel sides that are covered by a pair of plates 12A, 12B or similar protective body parts that include two flat portions. Although each plate 12A or 12B is illustrated as a one-piece element, the option is also available to combine two or more flat containment pieces that can limit the expansion of the pouch 2 while being more or less displaceable for the adjustment of the retraction stroke.

[0198] It will be understood by those skilled in the art that other variations and modifications can be readily made within the scope of the invention as claimed.

[0199] For example, while fastening elements 132, 133, 134 have been illustrated as being extended parts of casing 130, one or more of such fastening elements may alternatively be included in a tab or extension integral with bag 2'. A protective layer or outer envelope integral with bag 2' (i.e., an outer envelope that covers or encases the envelope of bag 2' that is in contact with the product) may optionally be provided in addition to or in place of casing 130.

[0200] Any reference signs in the following claims should not be construed as limiting the claims. It will be clear that the use of the verb "to comprise" and its conjugations does not exclude the presence of any other elements other than those defined in any claim. The word "a" or "an" preceding an element does not exclude the presence of a plurality of such elements. [Explanation of symbols]

[0201] 1. Freeze / Thaw Containment System 2 Flexible pouch 2' Bag 2r Reception Department 4 first transverse rib portion 6 Second transverse rib portion 7, 7' forward projection 8 Covering part 8a, 8b Margin area 10 Storage Units 12 Protective body 12A Lower Plate 12B Upper plate 15 Rectangular Frame 15a Inner Section 15b Outer Section 15c Corner Section 17 Connector 18 Mounting systems, mounting devices 18a First element: snap button 18b The second element: snap button 18o hole 21, 22 sheets 24 ports, forward ports 24' Port 31 Longitudinal covering parts, protective parts 32 Longitudinal covering parts, protective parts 35 Lid 35c snap button 41 Stopper 41', 42 Stopper 80 Periphery Margin 80a opening 81 End parts 82 Intermediate parts 83, 84, 85, 86 Ribs 91, 92, 93, 94 Profiles 94a, 94b Recess 102 Aperture 104a, 104b hose 110 Fixed elements 110a Protruding pin 110b Rim section 112 Protective body part 113 Clamp parts 113a surface 115 Foot 120a first end side, transverse side 120b second end side, transverse side 120c, 120d Longitudinal side 130 Casing 131 Side wall 132, 133, 134 Fastening elements 136, 137, 138 Aperture, anchor fixing member 146, 147, 148 Fastening members 146', 147', 148' Fastening members, anchor fixing members 160 Anchor Fixing Relief 162 Abutting end 200 Storage Parts 212 Protective body part 800 Ribs A Pouch Longitudinal Axis B1, B2 bulge B12, B12' embossed part, boss part BG Blocking groove BL Belt Line BS, BS2 Contact rim, contact surface C center C1, C2, C1', C2' corner ribs CC Crimping Ring CF1 Cavity CP Cavity CR Corner Area DL1, DL2 Virtual diagonal E1 end E2 end F94 External surface F110 internal surface G1, G2 groove G9 Groove GS Groove H35 Hinge HR Retention and Sustainment Assembly IP insert piece J Periphery seal L Pouch length when empty L' Pouch length in filled state LP lower part LS1, LS2 Longitudinal Side MF1, MF2 fixing means MR intermediate area MS Mid Section P Protective body reference plane PM positioning member PP central panel PP1 Panel part, panel PP2 Panel part, panel Q Biopharmaceutical compositions, biopharmaceutical fluids R1, R2, R2', R3, R4 Ribs S Upper surface, outer surface, second surface S' lower surface, outer surface, first surface SU Sample Unit T Hose / Tube UP Upper part V3 Inner volume w Pouch width when empty w' Pouch width in filled state W1, W2 Main walls X Longitudinal direction X1 Longitudinal axis XY principal plane Y transverse direction Z vertical axis

Claims

1. 1. A freeze / thaw containment system for storing a biopharmaceutical composition, the freeze / thaw containment system comprising: - a flexible pouch of a first volume configured to contain the biopharmaceutical composition; - a storage unit for use in freezing, storing, and thawing the biopharmaceutical composition contained within the flexible pouch; - a bag of a second volume configured to store a composition representative of the biopharmaceutical composition, the second volume being less than the first volume; - a casing defining an inner volume for containing said bag in its filled state; Including, The storage unit comprises: - a protective body including two plates for protecting the flexible pouch, 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 including a first end side and a second end side respectively perpendicular to the longitudinal axis; - a mounting device for fastening the two plates, such that in an assembled state of the two plates, the protective body part includes a peripheral margin extending in an annular manner in a protective body part reference plane, the peripheral margin being provided with at least one opening capable of receiving at least one port of the flexible pouch; Including, The freeze / thaw containment system further includes a rigid peripheral part, the rigid peripheral part being adjacent to or overlapping the peripheral margin, the rigid peripheral part being provided with a mounting set including three separate support members for supporting the protective body portion; In the assembled state: - the protective body portion extends planarly along the protective body portion reference plane in an empty state of the flexible pouch; - the two plates form lower and upper surfaces, respectively, of the protective body part, at least one of the lower and upper surfaces being a storage unit outer surface; a freeze / thaw containment system, the casing including at least two fastening elements that cooperate with fastening members included in the mounting set and one of the storage unit outer surfaces to fasten the casing along the storage unit generally parallel to the protective body portion;

2. 2. The freeze / thaw containment system of claim 1, wherein the two plates are sufficiently flexible to allow the protective body to have a greater thickness in a central area than in peripheral areas relative to the protective body reference plane, the thickness being measured between the lower surface and the upper surface along a direction perpendicular to the protective body reference plane.

3. 10. The freeze / thaw containment system of claim 1, wherein the flexible pouch is sandwiched directly between the two plates that restrain the flexible pouch.

4. 4. The freeze / thaw containment system of claim 3, wherein the two plates are in two pieces.

5. The fastening member is in a first region adjacent a first of the two longitudinal sides; and at least one second region positioned away from the first side 13. The freeze / thaw containment system of claim 1 being dispensed.

6. The hard peripheral part is a frame having an upper surface extending above the protective body part and a lower surface extending below the protective body part, The casing is removably secured to the mounting set, the mounting set extending around three sides of the flexible pouch, and the fastening members include: - two fastening members distributed on the two longitudinal sides, the two fastening members extending completely above the protective body part and extending away from the two other sides; at least one fastening member integrally formed with one of the three separate support members or integrally formed with a corner section interconnecting two of the three separate support members; 2. The freeze / thaw containment system of claim 1, comprising:

7. 2. The freeze / thaw containment system of claim 1, wherein the fastening members are distributed over a frame including the three separate support members and configured for interlocking of the casing.

8. 2. The freeze / thaw containment system of claim 1, wherein two of the fastening members are integrally formed with two separate corner sections and are adapted to be distributed over a frame around the flexible pouch.

9. 8. The freeze / thaw containment system of claim 7, wherein the casing has a prismatic shape.

10. The casing has a parallelepiped shape, - a casing frame defining a casing opening for access to the inner volume of the casing; a lid configured to close said casing opening in a removable manner; 9. The freeze / thaw containment system of claim 8, further comprising:

11. 2. The freeze / thaw containment system of claim 1, wherein the bag is part of a bag unit including one or more openings or ports, at least one of which is formed as a closable tube to allow the bag to be filled or emptied, and wherein the bag and the closable tube are stored within the interior volume of the casing.

12. 11. The freeze / thaw containment system of claim 10, wherein the bag is part of a bag unit including one or more openings or ports, at least one of which is formed as a closable tube and allows the bag to be filled or emptied, and wherein the bag unit is contained within the interior volume in a closed state of the lid.

13. The casing has a lower surface, the lower surface faces an outer surface of the storage unit; 8. The freeze / thaw containment system of claim 7, wherein the lower surface extends parallel to the protective body reference plane in an empty state of the flexible pouch.

14. 8. The freeze / thaw containment system of claim 7, wherein the casing is made from a single piece of transparent plastic material.

15. The casing comprises: - a sidewall defining the inner volume; - two opposing tabs each having a base connected to said side wall portion, each of said two opposing tabs being part of said fastening element; 2. The freeze / thaw containment system of claim 1, comprising:

16. The freeze / thaw containment system comprises: - a tube connected to the flexible pouch and configured for liquid flow of the biopharmaceutical composition; and - a tubing holder for holding said tube; a frame provided with four sides forming said rigid peripheral part, said frame intersecting said protective body part reference plane and extending parallel to said protective body part reference plane, said frame being adapted to hold said protective body part directly or indirectly, at least two profiles being included in said frame and forming all or part of said four sides; Further comprising:

2. The freeze / thaw containment system of claim 1, wherein the tubing holder comprises at least one fixing element, which is elastically mounted on one of the at least two profiles and provided with a clamping part for holding the tube.

17. 17. The freeze / thaw containment system of claim 16, wherein the at least one fixing element is provided with one of the fastening members, the one of the fastening members being adjacent to the clamping part and / or superimposed on the clamping part.

18. The fastening member is formed as a coupling piece of the mounting set, - a support member for the rigid peripheral part; - the fastening element of the casing; 13. The freeze / thaw containment system of claim 1 , interposed between

19. 2. The freeze / thaw containment system of claim 1, wherein the casing fastened along the storage unit has a smaller size corresponding to a casing thickness measured perpendicular to the protective body reference plane, the casing thickness being less than the distance between the bag and the protective body reference plane.

20. 10. A method of assembling a freeze / thaw containment system according to claim 1, wherein the freeze / thaw containment system is a protective system for storing and withstanding freezing and thawing of a biopharmaceutical composition contained in a flexible pouch of the freeze / thaw containment system, the flexible pouch being of a first volume; The method comprises: - optionally sandwiching the flexible pouch between two plates of a protective body part with a covering portion distributed among the two plates to cover the flexible pouch, the protective body part being configured to protect the flexible pouch and comprising the two plates, the protective body part further having a longitudinal axis and comprising four sides, the four sides comprising two longitudinal sides extending parallel to the longitudinal axis and two other sides comprising a first end side and a second end side respectively perpendicular to the longitudinal axis; - using a mounting device for fastening the two plates such that in an assembled state of the two plates, the protective body part includes a peripheral margin extending annularly around the covering portion in a protective body part reference plane, the peripheral margin being provided with at least one opening for receiving at least one port of the flexible pouch; - providing a casing bounding an internal volume, a bag in a filled state extending into said internal volume, said bag being of a second volume and containing a composition representative of said biopharmaceutical composition, said second volume being lower than said first volume; Including, the protective body and the mounting device belong to a storage unit, and the assembled state is obtained after the two plates are arranged to sandwich the flexible pouch and after the casing is fastened to fastening members belonging either to a rigid peripheral part surrounding the protective body or to an outer surface of the storage unit formed by the protective body, In the assembled state, the two plates respectively form a lower surface and an upper surface of the protective body, at least one of the lower surface and the upper surface being an outer surface of the storage unit, and the casing faces the outer surface of the storage unit and has at least two fastening elements which cooperate with the fastening members so as to maintain and fix the casing along the storage unit parallel to the protective body.

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