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

Abstract

A protective device is provided, which includes two plates forming a rectangular protective body for sandwiching, restraining, and protecting a flexible pouch. The two plates are attached together at a peripheral margin. Each plate has an outer surface with ribs provided along the peripheral margin in a peripheral annular region of the covering part that receives the pouch. The peripheral margin is mounted within a support part of a frame, and a sliding positioning member is fixed to the peripheral margin so that the peripheral margin is guided and allowed to be displaced inward during filling of the pouch, while the protective body extends generally planarly at least in the panel parts surrounded by the ribs. This allows for gradual conformational changes of the protective body when filling the pouch with a biopharmaceutical product, while facilitating reverse displacement of the peripheral margin during drainage.

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 have to be protected, even though the risk of leakage is small.

[0005] Patent document 1 discloses a container for flexible pouches. The container includes a lower part and an upper part, which are rigid and joined along a common edge, forming 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] US Patent No. 5,999,366 provides a protective body, in which a flexible pouch is sandwiched by two plates of the protective body with a restraining effect. A freeze / thaw protection system can be obtained by combining such a protective body and a single-use flexible container wrapped by a protective shell. However, uniform fluid distribution may be difficult because in the filled state of the flexible container, a significant bulge (large belly) is formed in the middle. 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 of the inner volume of the pouch.

[0009] Moreover, some radial / transverse folds or waves may form on the pouch outer surface during filling, which may interfere with proper fluid distribution, especially in the four corner regions.

[0010] US Patent No. 5,399,633 discloses a single-use flexible freezer bag, in which a tufting coupling is provided to divide the cavity of the container into several regions. This is of interest to limit the risk of having significant bulges, so that concentration of liquid mass is prevented in the intermediate parts of the flexible container. Such a design cannot be widely used, especially because the bag design becomes more complicated, which increases the cost of the single-use container. Moreover, this kind of container cannot extend in a plane in the empty state and may become more difficult to drain, especially when the container is filled with a large volume of fluid. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] European Patent Application Publication No. 2322442 [Patent Document 2] US Patent Application Publication No. 2018 / 125757 [Patent Document 3] International Publication No. 2015 / 200218 Brochure [Patent Document 4] International Publication No. 03 / 037082 Brochure Summary of the Invention [Problem to be solved by the invention]

[0012] The object of the present invention is to provide a protection device for obtaining a robust freeze / thaw containment and protection system that is efficient in limiting the concentration of liquid mass in intermediate areas of a flexible pouch (typically a 2D pouch that expands in the filled state) while maintaining design flexibility for the flexible pouch. [Means for solving the problem]

[0013] To this end, an embodiment of the invention is a protective device for use in freezing, storing, and thawing biopharmaceutical materials contained within a flexible pouch, the protective device comprising: - 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 system for fastening two plates, such that in an assembled state of the two plates, the protective body part includes a peripheral margin extending annularly in a reference plane of the protective body part, the peripheral margin being provided with at least one opening capable of receiving at least one port of a flexible pouch; Including, The two plates define two mutually unfixed opposing parts forming a covering part for covering the flexible pouch, the covering part being surrounded by a peripheral margin; 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 are configured to clamp the flexible pouch to constrain the flexible pouch in a filled state of the flexible pouch, and the protective body part is deformable due to contraction of the two plates in at least one direction belonging to a protective body part reference plane; The protective device provides two plates forming first and second outer surfaces, respectively, of a protective body portion facing in opposite directions, at least one of the first and second outer surfaces being a surface having a plurality of ribs, the plurality of ribs extending along a peripheral margin and over at least a peripheral annular region of the covering part.

[0014] By such a rib pattern, the geometry of the protection device in the filled state of the pouches restrained by the plate can be favorably influenced: for large volumes (e.g., about 50 liters, 75 liters or more), fully encircling ribs or a similar rib pattern parallel to the peripheral margins can prevent the formation of undesirable waves, which create dead volume and impair efficient drainage operation.

[0015] More generally, the ribs can locally structure the plates (preferably two plates) near the peripheral margin, preventing undesired folding / bending of the plates while still allowing the protective body to expand due to the filling of the pouches stored therein. The ribs can thus be, for example, ribs arranged to locally structure the covering part of the protective body around a panel part (which can be provided in a substantially rectangular or square shape).

[0016] A good compromise can be obtained between the ease of the covering parts to expand transversely (or vertically when the protective body reference plane is horizontal) and adequate flexibility of the plate used, while also preventing fold formation near the peripheral margin. The plate can be accordion-like, using several ribs arranged parallel to each of the four marginal parts of the peripheral margin.

[0017] An accordion effect in the plate may be obtained by having parallel ribs, each of which has a locally lower thickness than the rest of the plate, which may help to have a greater expansion in the direction transverse (perpendicular) to the protective body reference plane when a fluid-filled pouch restrains the inner face of the plate (where the ribs define elongated hollows or grooves), despite the lower flexibility of the plate material compared to the plastic material of the pouch.

[0018] Each rib of the plate may be obtained by locally drawing the plastic material, thus causing a reduction in thickness at the rib. This may be a deep drawing that is deep enough to make the hollow or groove of each rib deeper than the average thickness of the plate. Each of the ribs may have a flared shape, typically forming a U-shaped profile in cross section (cross section transverse to the length of the rib).

[0019] The depth or height of the ribs can be at least two or three times the thickness of the plate (plate material thickness), preferably at least four times or more. With such height and with a slight reduction in thickness, the ribs located near the peripheral margin effectively improve the expansion near the marginal portion (with a higher shift relative to the protective body reference plane) as if the plate were locally more expandable. Even if the marginal portion cannot expand due to the attachment system, all or part of the peripheral annular region can expand / displace from the protective body reference plane more rapidly than if the plate were deprived of such ribs.

[0020] The grooves formed by the ribs are elongated, such grooves having a groove length corresponding either to the lengthwise extension or to the widthwise extension of the plate (which is generally a rectangular plate). The groove internal width can be greater than 10 mm, preferably greater than or equal to 15 mm. In some embodiments, such width is between 20 mm and 40 mm. As is evident in Figures 5A, 5B, a wavy profile can be obtained due to the groove (between the panel part and the peripheral margin) before any filling operation.

[0021] The ribbed area can be an annular area formed as a transition area between the non-ribbed panel part and the peripheral margin, which is typically not allowed to move transversely relative to the protective body reference plane, such a transition area can form a homogeneous sloped area in the expanded / filled state of the system, preventing the formation of undesirable waves / folds.

[0022] The peripheral margin is configured to remain flat along the protective body reference plane in the assembled state independent of the filling state of the flexible pouch covered by the covering part. Optionally, the attachment system can be a fastening assembly, and the two opposite sides (opposite margin portions) of the peripheral margin are part of the fastening assembly for preventing any shifting movement of position between the two plates when the two plates are fastened to each other at at least two margin portions in a predefined overlapping configuration to form the protective body.

[0023] The plates are typically separate pieces, preferably two pieces. The constraining effect is of interest for the step of emptying the flexible pouch, and is also advantageous in limiting the vertical expansion of the fluid, especially during freezing, when the protective body reference plane extends substantially horizontally.

[0024] Vertical expansion can optionally also be limited by having a belt effect exerted on the intermediate region of the covering part, possibly by sustaining a contraction stroke of the peripheral margin, at intermediate margin portions located on either side of this intermediate region.

[0025] In some embodiments, the ribs of the plurality of ribs are distributed over at least two opposite parts of the surface, said opposite parts being longitudinally opposite.

[0026] Moreover, a rib of the plurality of ribs includes one or more first transverse rib portions proximate or adjacent to the first end side and one or more second transverse rib portions proximate or adjacent to the second end side.

[0027] In various embodiments of the device, optionally, one or more of the following arrangements may be relied upon: the one or more first transverse rib portions include two first transverse rib portions, while the one or more second transverse rib portions include two second transverse rib portions. - The attachment between the plates is a removable attachment, allowing the plates to be completely separated. The plates are removably fixed to one another by means of a mounting system that is (selectively) distributed on the peripheral margins. - Two opposite margin portions (provided longitudinally at the peripheral margin) are part of the fastening assembly for preventing any shifting movement of position between the two plates when the two plates are fastened to each other at at least the two margin portions in a predetermined overlapping configuration to form a protective body part. - each of the two plates includes embossments or boss portions which, in the assembled state of the plates (to form the protective body), define several protective body embossments which protrude in a first direction perpendicular to the protective body reference plane and form corresponding cavities which open in a second direction opposite to the first direction. The embossings may be distributed longitudinally at the peripheral margin. - the number of embossments provided in one of the two plates is engaged with the same number of corresponding cavities provided in the other of the two plates. - 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 and has a shrinkage profile at the periphery of the protective body part, optionally in the marginal portion, whereby 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 member can be a slider or similar member housed within a guide or covering part of the holding and sustaining assembly, which forms a stationary frame around the hollow space / location for the pouch. - each of the positioning members may have an insertion pin or member, which is either inserted into a protective body through-slot or into a hollow part bounded by a pair of respective embossings of the two plates (the slot or hollow part being provided at the peripheral margin so as not to interfere with the expansion of the covering part covering the pouch); a rib of the plurality of ribs further comprises a group of elongated rib portions, the elongated rib portions extending in a peripheral annular region of the covering part; The elongate ribs may be parallel to the longitudinal axis and therefore extend perpendicular to any one of the first transverse rib portion and the second transverse rib portion. - The group of elongated rib portions may be composed of longitudinal ribs and / or may include two opposing elongated rib portions / ribs that are longer than any one of the first transverse rib portion and the second transverse rib portion. - each plate is provided with clearance areas (that is areas without any relief / ribs) provided between and / or separating the longitudinal rib portions distributed in each half of the plate. Each plate has one or two pairs of elongated continuous rib portions parallel to the longitudinal axis, which extend across a mid-section or mid-transverse band of the plate. - the elongated continuous rib portion typically extends longitudinally so as to remain close only to a distance of less than about 30 mm or less than 50 mm from each one of the two opposing margin portions of the rectangular peripheral margin, while the transverse distance between the two opposing margin portions is at least equal to 500 mm or 600 mm, and preferably greater than or equal to 700 mm, when the plates extend in a planar manner (this planar state is obtained for the unfilled state of the pouch when the plates are assembled to clamp the pouch). - Of each pair of elongated continuous rib portions parallel to the longitudinal axis extending across the intermediate section or intermediate transverse band of the plate, each elongated continuous rib extends straight so as to remain close to its marginal portion at a distance from said marginal portion less than 10% of the total plate width. - The plate has longitudinal rib portions of relatively short length compared to the elongated continuous rib portions (also called side rib portions) crossing above the mid-section / mid-transverse band, and the relatively shorter longitudinal rib portions do not interfere with the clearance areas or with the plate intermediate areas which are provided with only transverse rib portions. The corner ribs include a first corner rib interconnecting one of the elongated rib portions with one of the first transverse rib portions. The corner rib further includes a second corner rib interconnecting one of the elongated rib portions with one of the second transverse rib portions. - in a surface provided with a plurality of ribs, a continuous rectangular area without ribs is surrounded by (and, in some cases, is bounded between) a first group of ribs and a second group of ribs, the first group of ribs extending annularly in a peripheral annular area of ​​the covered part and the second group of ribs extending parallel to the first group of ribs and being positioned closer to the peripheral margin compared to the first group. - a first group of ribs may extend annularly at a maximum distance from the peripheral margin (which is a first distance), while a second group of ribs may extend at a minimum distance from the peripheral margin (which is a second distance), the second distance typically being greater than the first distance.

[0028] In some embodiments, the protective body portion can extend substantially horizontally and / or a first outer surface bounded by a peripheral margin is a lower surface of the protective body portion, while a second outer surface bounded by a peripheral margin is an upper surface of the protective body portion.

[0029] In certain embodiments, each of the lower and upper surfaces includes a pattern of ribs distributed among two halves, with a first transverse rib portion being provided in a first of the two halves, while a second transverse rib portion is provided in a second of the two halves.

[0030] Optionally, the pattern of ribs in the lower surface and the pattern of ribs in the upper surface are symmetrical with respect to a protective body reference plane, and the two halves are preferably two symmetrical halves with respect to a central plane perpendicular to the protective body reference plane.

[0031] In some embodiments, the rib pattern surrounds at least one smooth panel region that extends away from the peripheral margin.

[0032] Around the panel, one or two continuous or discontinuous ribs of the rib pattern are configured to allow fluid (liquid) to spread to the edges and corners. In an embodiment, the ribbed pattern provides more flexibility to the protective body edge regions (areas adjacent to each of the four side edges) that are subject to deformation by forming sloped portions parallel to the peripheral margin. Such ribs that define the boundaries of the panel can be continuous or discontinuous annular ribs.

[0033] The longitudinal ribs (elongated) are capable of propagating a hinge effect at the joint (which can be a straight joint) between the peripheral margin where the plate remains fixed in the plane and one of the long sides of the four sides of the rectangular covering part.

[0034] The transverse ribs (typically also elongated) can propagate the unfolding with a hinge effect at the joint (which can be a straight joint) between the peripheral margin where the plate remains fixed in plane and one of the short sides of the four sides of the rectangular covering part.

[0035] In various embodiments of the device, optionally, one or more of the following arrangements may be relied upon: The protective body portion is provided with ribs on a first outer surface and on a second outer surface, such that a first plurality of ribs are formed on the first outer surface and a second plurality of ribs are formed on the second outer surface. - the protective body is configured to expand along a direction perpendicular to the body reference plane due to filling of the flexible pouch sandwiched between the two plates, such that two mutually unfixed opposing parts form respective panels, each extending parallel to the protective body reference plane and surrounded by an elongated relief extending parallel to a peripheral margin. The relief may be formed by part of a rib which can protrude outwards and which is included in the protective body part. each of the two plates includes at least one plate panel part extending between a first transverse rib portion and a second transverse rib portion; A single panel may be formed by the outer surfaces of each plate being provided with ribs. Two panel portions, distributed longitudinally, may be formed by respective plate outer surfaces which are provided with ribs. Each of the two plates has at least one central portion that is spaced apart from the two end sides. - one or two ribs may extend transversely and separate two panel parts in the same plate, such ribs typically extending transversely in such central portion. - Each panel part is formed without ribs or hinge lines. - In the unfilled state of the pouch, or in any flat state of the protective device, the first and second outer surfaces of each have a height difference of between 0.8 mm and 20 mm (and do not protrude further). - A maximum height relief is provided in an area encompassing one or two panel parts, while no height differences are found among the panel parts.

[0036] In some embodiments, the protective device may be provided with a retaining and sustaining assembly (separate from the mounting system) for supporting the protective body at the peripheral margin, away from any one of the ribs of the protective body. Typically, the retaining and sustaining assembly may include a frame with an abutment surface arranged between the covering part and the peripheral margin, such that it allows the two plates to move, expand and contract in a transverse direction belonging to the protective body reference plane, without the peripheral margin being displaced inwards beyond the abutment surface.

[0037] In various embodiments of the protection device, optionally one or more of the following arrangements may be relied upon: The peripheral margin is provided with a positioning member spaced from any one of the ribs of the protective body portion. - The positioning member is configured to limit transverse movement of at least one part of the peripheral margin and to limit expansion of the flexible pouch in at least one region intermediate between the first transverse rib portion and the second transverse rib portion. - the first transverse rib portion is typically proximal to the first end side and distal to the second end side, while the second transverse rib portion is proximal to the second end side and distal to the first end side (preferably the first transverse rib portion is not spaced apart from the corresponding first end side by a distance greater than 15% or 25% of the total length of the plate when measured along the longitudinal axis in the planar empty state; similarly, the second transverse rib portion may not be spaced apart from the corresponding second end side by a distance greater than 15% or 25% of the total length of the plate when measured along the longitudinal axis in the planar empty state). - each of the first transverse rib portion and the second transverse rib portion extends perpendicular to the longitudinal axis and belongs to an intermediate region between two corner regions respectively adjacent to the intersection of two of the four sides; the two corner regions are configured to be more elastically deformable than the intermediate region provided with the first transverse rib portion and the intermediate region provided with the second transverse rib portion. Each intermediate region is adjacent to one of the first end side and the second end side. - each of the first outer surface and the second outer surface includes a longitudinal rib portion extending parallel to the longitudinal axis in two opposing side regions, each proximal to the peripheral margin and distal to the longitudinal axis. Each of the corner regions is formed to be more elastically deformable than any one of the side regions provided with longitudinal rib portions.

[0038] In some embodiments, each plate may be provided with several ribs that project outwardly (i.e., project upwards for the upper plate and project downwards for the lower plate). The ribs closer to the peripheral margin (so-called side ribs) may project more than any other ribs present in the plate.

[0039] The maximum of the height (protruding height) is obtained at the side ribs, while the minimum of the rib height can optionally be obtained at the corner regions.

[0040] Each of the lower and upper surfaces has a planar surface, while the height of the ribs or similar protruding portions protruding from the planar surface is large (e.g., greater than 6 mm or 10 mm) only in areas away from two imaginary diagonals provided on the respective plates, which are rectangular in shape.

[0041] In some embodiments, the protective body portion can include: - the two plates are made as two separate pieces having the same perimeter size and the same outer shape, and each of the first outer surface and the second outer surface includes a first transverse rib portion proximate the first end side and a second transverse rib portion proximate the second end side. - The two plates can be two separate identical pieces. - The ribs and protective body are made from the same freeze resistant polyester or copolyester material, and the two plates are two separate pieces. - The plate material is not brittle at about 25°F or -4°C, and the material is preferably PET or TRITAN. - the two plates are made from a deformable plastic that is harder than the flexible pouch and are configured such that the gap between the two plates, when measured perpendicular to the protective body reference plane in the filled state of the flexible pouch, increases with increasing distance from the peripheral margin. - The protective body part is expandable with the corner areas not being reinforced by ribs. Each rib of the plurality of ribs defines an inwardly opening interior hollow portion and is adapted to open towards the flexible pouch. Each rib of the plurality of ribs defines an interior hollow portion that is separate from the peripheral margin, such that the interior hollow portion provides additional volume in the gap between the two plates. - each of the two plates is a plate having a rectangular shape with four corners and two imaginary diagonals, the two imaginary diagonals intersecting a pair of corner vertices of the four corners respectively, each of the two imaginary diagonals intersecting a first series of corner ribs and a second series of corner ribs, the first series of corner ribs being proximal to a first end side and projecting outwardly along a direction perpendicular to the protective body reference plane, and the second series of corner ribs being proximal to a second end side and projecting outwardly along a direction perpendicular to the protective body reference plane. - Each of the corner ribs is curved and connects two rib sections that are perpendicular to each other. The first transverse rib portion may be directly connected to a first series of corner ribs, while the second transverse rib portion may be directly connected to a second series of corner ribs.

[0042] Also, an embodiment of the present invention is a freeze / thaw containment system for storing a biopharmaceutical composition, the freeze / thaw containment system comprising: A protection device according to the invention; a flexible pouch sandwiched between two plates, the flexible pouch being fillable with a biopharmaceutical composition through at least one port in the flexible pouch projecting outwardly through at least one opening, the flexible pouch being more flexible than the material of the protective body; The present invention provides a freeze / thaw containment system comprising:

[0043] In some embodiments, the two plates constrain the flexible pouch by means of a covering part extending between the two marginal portions of the peripheral margin.

[0044] The system may be provided with a frame for selectively mounting the protective device at the peripheral margin. The frame thus allows the covering part of the protective body to be suspended, since only the peripheral margin is fixed to and sustained by the frame. In some options, the frame is rectangular and does not cover the covering part. In other parts, all or part of the frame may be included in a protective shell provided with a shell part forming a housing for receiving the covering part. Such a protective shell preferably includes all or part of the mounting system, thus allowing the peripheral margin to be maintained in the protective body reference plane, which typically coincides with the gap provided by the frame.

[0045] The frame may in some embodiments be provided with upper and lower parts, which are assembled to form a frame with retention features for the peripheral margin. The positioning members may be provided either on the peripheral margin or may be included within the parts of the frame.

[0046] A freeze / thaw containment system, which is a protective system for storing a biopharmaceutical composition contained in a flexible pouch and for withstanding freezing and thawing thereof, can be assembled using a method comprising the following steps: - sandwiching the flexible pouch between two plates of a protective body part, optionally with covering parts distributed among the two plates to cover the flexible pouch, 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; - fastening the two plates by means of a mounting device at a peripheral margin such that in the assembled state of the two plates the protective body has a peripheral margin extending annularly around the covering part in a protective body reference plane; - inserting at least one port of the flexible pouch into the at least one opening through the peripheral margin (so that it is received within such at least one opening); - maintaining the peripheral margin parallel to the protective body reference plane by a holding and sustaining assembly that houses the peripheral margin in an annular housing, such that the peripheral margin remains flat along the protective body reference plane in the assembled state independent of the filling state of the flexible pouch covered by the covering part; Including, In assembled state: the two plates are configured to clamp the flexible pouch to restrain the flexible pouch in a filled state of the flexible pouch; The two plates form a first outer surface and an upper surface, respectively, of the protective body part, at least one of which is a surface having a plurality of ribs that extend along a peripheral margin and over at least a peripheral annular area of ​​the covering part, so as to locally structure the covering part of the protective body part.

[0047] It can be easy to assemble, in which ribs are provided protruding outwards, these ribs being distributed on two opposite parts of the surface, being longitudinally opposite parts.

[0048] The protective body portion may be less ribbed or may be provided with reduced height relief in four corner regions of the protective body portion, each adjacent the intersection of two of the four sides.

[0049] The flexible pouch is expanded when filling the flexible pouch with the biopharmaceutical composition in a fluid state, and the covering part restrains the flexible pouch while being guided as it expands due to the side ribs that prevent undesired centripetal folding near the peripheral margins.

[0050] 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]

[0051] [Figure 1] FIG. 1 is a perspective view of a protection device according to a first embodiment of the invention, before assembling the two plates of the protective body. [Figure 2A] FIG. 2 is a top view showing the assembled protective device of FIG. 1, in which a ribbed pattern is provided on the outer surface (here, the upper surface) of the protective body portion, including ribbed portions of lower height at the corners. [Figure 2B]FIG. 2 is a diagram showing a portion of the protective device of FIG. 1 taken horizontally along a plane parallel to the protective body reference plane, where the cuts are made above the corner rib portions and below the other rib portions to illustrate that all ribs formed on the plate outer surface define corresponding internal recesses or grooves that open inwardly. [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 of a system for storing biopharmaceutical fluids according to an embodiment of the present invention in a configuration with a protective body portion disassembled. [Figure 5A] FIG. 4 shows a detail of a relief provided in a plate as included in the system of FIG. 3 and used to form a storage unit according to a second embodiment of the invention. [Figure 5B] FIG. 4 shows a detail of a relief provided in a plate as included in the system of FIG. 3 and used to form a storage unit according to a second embodiment of the invention. [Figure 5C] FIG. 4 shows a detail of a relief provided in a plate as included in the system of FIG. 3 and used to form a storage unit according to a second embodiment of the invention. [Figure 5D] FIG. 4 shows a detail of a relief provided in a plate as included in the system of FIG. 3 and used to form a storage unit according to a second embodiment of the invention. [Figure 6] FIG. 1 is a perspective view showing a complete 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 7]FIG. 7 is a perspective view similar to FIG. 6, but with some of the internal positioning members adjusted to selectively limit displacement and contraction of the plate in an intermediate region of the protective body, and the plate being provided with a first ribbed pattern that promotes fluid displacement toward the corners. [Figure 8] FIG. 8 is a perspective view similar to FIG. 7, but similarly with some of the internal positioning members adjusted to selectively limit plate displacement and contraction in the intermediate region of the protective body, but with a second ribbed pattern that promotes fluid displacement toward the corners. [Figure 9] 8A-8C illustrate an exemplary distribution of positioning members around the protective body portion when using a frame such as that shown in FIGS. 6-7. [Figure 10A] 13 is a vertical cutaway view showing a positioning member suitable for forming a stopper configured to slide inwardly into the profile cavity while retaining a portion of the peripheral margin of the protective body portion. FIG. [Figure 10B] FIG. 10B is the same vertical cutaway view as FIG. 10A, showing the abutment position, where the positioning members have stopped inward movement of the corresponding peripheral margin portions of the protective body portions. [Figure 11A] 13A-13D illustrate respective steps performed in forming a frame for handling and storing protective devices including positioning members, with the optional step of fastening feet to define stackable shelf modules. [Figure 11B] 13A-13D illustrate respective steps performed in forming a frame for handling and storing protective devices including positioning members, with the optional step of fastening feet to define stackable shelf modules. [Figure 11C] 13A-13D illustrate respective steps performed in forming a frame for handling and storing protective devices including positioning members, with the optional step of fastening feet to define stackable shelf modules. [Figure 12] 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 protective device in the filled state of the flexible pouch. [Figure 13A] FIG. 2 is a top view of a flexible pouch filled with liquid inside a protective device, without showing the protective body portion and positioning member. [Figure 13B] FIG. 9 is a side view showing a frame-like holder and flexible pouch filled with liquid inside the system of FIG. 7 or FIG. 8, without showing the protective body portion and positioning member. [Figure 14A] FIG. 13A illustrates diagrammatically the evolution of the plate profile (pouch not shown) at different filling levels with ribbed portions that help to spread more liquid towards the edges. [Figure 14B] FIG. 13 illustrates the synergistic effect of combining a ribbed pattern and a belt effect for high levels of pouch filling. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0052] In the various drawings, the same reference symbols are used to designate identical or similar elements.

[0053] In the different figures, the vertical, longitudinal and lateral directions are based on the freeze / thaw storage system being stored horizontally in shelves. The direction perpendicular to the longitudinal direction is the lateral direction. One direction through the height of the freeze / thaw storage system 1 is the vertical direction, which is reflected by the direction Z, inter alia, in Figures 4 and 6-8.

[0054] In an embodiment, the freeze / thaw containment system 1 can be as illustrated in Figures 3, 4 or 6, 7 or 8 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).

[0055] Thus, when the biopharmaceutical composition Q is frozen, the storage area 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 dimension (along the longitudinal axis X1) of the protective body portion 12 is slightly reduced. In this case, the biopharmaceutical composition is slightly constrained by the two plates 12A, 12B.

[0056] According to the embodiments, the plate dimensional reduction (when considered in the XY plane) is obtained by the profile of the shrinkage stroke, which is adjusted differently depending on the longitudinal position of some positioning members PM integral with the marginal parts of the protective body part which locally prevent or limit such dimensional reduction, for control of the shrinkage stroke, as will be explained below. Additionally or alternatively, a rib pattern is provided to control which shrinkage is obtained without reducing the height of the pouch sides or without changing the optimal shape of the pouch 2.

[0057] 1, 3 and 4, the protective body 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 12, 112 here typically includes ribs R1, R2, R2', R3, R4 on each plate 12A, 12B. The two plates 12A, 12B can be two pieces, which preferably define the protective body 12, 112 without any additional pieces. More generally, only two pieces can form the covering part 8 that receives the pouch 2.

[0058] The protective body part 12, 112, 212 is obtained by fastening the two plates 12A, 12B at the peripheral part surrounding the covering part 8 of 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 part 8 clamps 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 margin parts 8a, 8b of the plates. The respective margin parts 8a, 8b can be composed of the four outer band areas of the plates 12A and 12B.

[0059] The protective body part 12, 112, 212 extends planarly along the protective body part reference plane P and cannot expand like a thin rubber balloon, because the plates 12A, 12B are relatively rigid to restrain the pouch 2. The protective body part 12, 112, 212 is typically as rigid as a PET bottle for storing carbonated water or may be even rigider, thus allowing very limited deformations compared to the material of the flexible pouch 2. In the plates 12A, 12B, the ribs R1, R2, R2', 800 also structure the covering part 8 in its peripheral annular region 8p, typically along the peripheral margin 80, so as to have a guiding effect when the protective body part 12 expands. Since only linear regions for local / linear reinforcement are provided, the structuring does not impair the expansion, but allows the plate deviation angle α as shown in FIG. 10B to be sufficiently high. For example, such angle α is greater than 25° or 30° with respect to the reference plane P in a fully filled state of the pouch 2 clamped by the plates 12A, 12B.

[0060] In the illustrated embodiment of Figures 1, 2A-2B, rib R1 and ribs R2, R2' may be spaced apart and parallel in the ribbed pattern of plate 12A or 12B so as to delimit a continuous rectangular area therebetween in the absence of the ribs. Rib R1 is closer to the peripheral margin 80 compared to R2, R2', and rib R1 may form a continuous rectangular rib pattern, possibly with rounded corner ribs (curved rib portions). Rib R1 may thus be included within a continuous rectangular rib, which is broken down into two opposing transverse rib portions 4, 6 and two elongated longitudinal rib portions 110, possibly with four corner ribs interconnecting each transverse rib portion to the two longitudinal rib portions 110.

[0061] Ribs R3 and / or R4 may optionally be added, with a shift towards the middle region compared to the side ribs R1 or ribs R, R2'. Thus, at least three transverse rib portions extending perpendicular to the longitudinal axis X1 of the protective body part 12 may be provided at opposite ends of each of the plates 12A and / or 12B.

[0062] 1, 2A-2B, 4 and 7, it can be seen that the transverse rib portions 4, 6 are contained in U-shaped ribs R2, R2', R3, R4, the "U" opening towards the central region to the corresponding outer surface S or S'. The shape and location of these ribs R2, R2', R3, R4 are suitable to obtain a guiding or "pushing" effect to have more liquid composition Q near the peripheral margin 80.

[0063] When the belt effect is obtained as described below (with reference to Figures 13A-13B), a locally lower height can optionally be provided in the intermediate part 110a of each longitudinal rib portion 110, for example as illustrated in Figures 3 and 5C.

[0064] The system 1 is suitable for storing and freezing / thawing the biopharmaceutical composition Q (see FIG. 10B). With reference to FIGS. 4, 6 and 10A-10B, such a system 1 is here horizontal, using a horizontal frame. However, the system can also be vertical in a variant, such that the pouch 2 can be stored vertically in the cavity of a vertical frame-like holder (see for example the pouch described in US Pat. No. 5,399,433, which is received vertically by the use of a rigid slotted frame). The use of a rectangular frame 15 (provided with an inwardly opening slot or cavity CP) can be of interest, in order to form a compact holder capable of accommodating the respective marginal parts of the protection device 10. When the pouch 2 and the protection device 10 are together held, a storage unit (forming the entire system 1) is obtained, allowing efficient protection of the biopharmaceutical composition Q.

[0065] 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 or FIG. 4 (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 more 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.

[0066] 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 plates 12A, 12B, where it cannot be removed without removing at least one of the two plates 12A, 12B, by detaching the plate margin portion 8a from the plate margin portion 8b (the plates are fixed between them without any specific fixation between the pouch 2 and any one of the plates). 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. The assembly HR is here provided with a frame 15 which includes a slide SL or similar slotted structure for holding the protection device 10 at its peripheral margin 80 .

[0067] Typically, the receiving portion 2r of the storage pouch 2 for receiving the biopharmaceutical composition Q cannot come into contact with the rigid structure of the holding and sustaining assembly HR thanks to the protective body portion 12, 112, or 212. In the assembled state, the protective body portion 12, 112, 212 completely covers the receiving portion 2r of the pouch 2, while the peripheral margin 80 remains planar (here, due to the mounting system 18, always coincident with the reference plane P).

[0068] The protective device 10 provides efficient protection during freezing, storage 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 not as flexible as 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.

[0069] Each pouch 2 can be filled with a solution (fluid composition) that will be frozen and held with slight compression between the two plates 12A, 12B that serve as heat exchange surfaces. For this purpose, the plates completely cover the pouch 2 at least in the fluid receiving portion, 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 the optional outer extension). In the illustrated embodiment, the pouch 2 is completely covered by a protective body portion 12, 112 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 Fig. 6, Fig. 7 or Fig. 8).

[0070] Arrangement for maintaining and guiding a protective body part The pouch 2 sandwiched between the plates 12A and 12B may be supported by a structure surrounding the pouch. Such a structure may include a frame 15 or similar holding and sustaining device HR, which is arranged around the covering part 8 to prevent damage to the inner material during handling and transport. Referring to Figs. 6-8, the frame 15 may be a rigid part of the support structure. Here, the frame 15 may be a modular part of a device or shelf that may be positioned in the freezer. Rollers (not shown) may 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 the four protective sides of the protective device 10.

[0071] The frame 15 may be included in a retaining and sustaining assembly HR, which also includes a positioning member PM engaged with a peripheral margin 80 of the protective body portion 12, as shown inter alia in Figures 9 and 10A-10B. The assembly may include a plurality of feet 115, possibly of a tubular shape, suitable for stacking. Figure 11C illustrates a non-limiting example of the integration of feet 115 suitable for obtaining a shelf structure.

[0072] More generally, the protective body part 12 and the retaining and sustaining assembly HR may be assembled such that 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 placed inside the storage assembly, the pouch 2 being covered by the two plates 12A, 12B. As shown in FIG. 3 among others, the protective body part 12 has a peripheral portion 80 that is engaged in the gap of the retaining and sustaining assembly HR. The protective device 10 is suitable for use in freezing, storing and thawing biopharmaceutical fluids stored in the flexible pouch 2, the fluids being typically introduced after obtaining the entire system 1 for restraining and retaining the flexible pouch 2 (which is typically a disposable pouch).

[0073] The freeze / thaw containment system 1 is provided with several positioning members PM, which are fixed to or formed on this peripheral margin 80. This peripheral margin 80 can be seen as part of the protective body, which is complementary to the covering part 8, where the pouch conformation changes depending on the level of filling of the pouch 2. The system 1 also comprises a frame 15, which is constructed to surround the hollow space in which the pouch 2 extends. The frame 15 can be provided with two longitudinal support parts, which are separate from the positioning members PM.

[0074] It will be appreciated that the frame-protective body interface is shifted with respect to the covering part 8 and therefore does not interfere with expansion along the Z direction. Moreover, the ribs of the plates 12A, 12B can be formed away from the arrangement provided to maintain the protective body 12, 112, since only the peripheral margin 80 includes or is in contact with the positioning member PM.

[0075] 9 to 12, the positioning member PM can be part of the mounting system 18 and / or participate to clamp the two plates 12A, 12B of the protective body part at the peripheral margin 80. The positioning member PM can be composed of at least two pieces, which are distinguishable and separate from the pouch 2 and the plates 12A, 12B, where they include a pair of flat bars, possibly clamping the plates 12A, 12B when using an insert piece IP (e.g. a screw-in element for assembling the flat bars, etc.), forming the positioning member PM. More generally, the positioning member PM can be a rigid part, which is typically made of a plastic material (e.g. HDPE) and is provided with fastening pieces or integrated fastening means.

[0076] The positioning member PM is configured to protrude from at least one of the lower surface S' and the upper surface S, respectively, of the protective body part 12, 112, 212 at a peripheral margin 80. Typically, the positioning member PM comprises a lower part LP and an upper part UP, respectively, which are two separate flat bars or any suitable pair of pieces configured to clamp the protective body part in the area of ​​the peripheral margin 80, outside the hollow space of the frame 15 through which the pouch 2 extends.

[0077] 10A, the forward projecting parts 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 part material, since the profiles 91, 92, 93, 94 are typically made of harder material (e.g. steel, metal, aluminum or hard plastic).

[0078] In the system shown in Figures 9 and 10A-10B, the protective device 10 can be obtained with the protective body part 12, 112, 212 not being removable from the frame 15, which, when assembled, is understood to have a U-shaped or rectangular shape surrounding the pouch 2 stored in the protective body part. In fact, the positioning members PM provided in the peripheral margin 80 or already fixed thereto can be housed / persisted in the respective parts or profiles 91, 92, 93, 94 of the frame 15. Here, the fastenings are adapted to allow the protective body part to move, extend and contract along the protective body part reference plane P, i.e. to provide a degree of freedom along at least one of the directions of the axes X and Y shown in Figures 1, 4 and 6-8.

[0079] The use of four rigid profiles is illustrated here in Figures 11A-11C for forming a frame 15, which is of interest for forming an efficient rectangular frame 15 for protective purposes. Optionally, the pouch 2 can be of the Flexboy® type and thus a sterile single-use disposable container, which is adapted to be clamped by a protective body part and to be surrounded by the frame 15, which is obtained after assembling the profiles 91, 92, 93, 94 or similar holding elements.

[0080] 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).

[0081] When the positioning member PM is part of the mounting system 18, the mounting system 18 can be considered as an assembly of several displaceable parts that can move inwardly relative to the frame 15. Here, the frame 15 includes two elongated longitudinal support parts formed by two pieces or profiles 93, 94, each defining a housing for accommodating the respective positioning member PM. At least one of the positioning members PM constitutes a slider that is inwardly movable inside the corresponding housing. With reference to Figs. 10A-10B, it can be seen that in the clamping area of ​​the peripheral margin 80, the respective lower part LP and upper part UP are two separate pieces that are configured to clamp the protective body part. The respective clamping area can be elongated parallel to the protective body part edge by extending in the longitudinal direction to be at least four times longer (with a length L8) than the maximum width W8 of the positioning member PM, as illustrated in particular in the non-limiting embodiment of Fig. 11A.

[0082] 10A-10B, all or part of the frame 15 forms a holding and sustaining assembly HR. This assembly HR has surfaces BS1, BS2 for the abutment of the positioning member PM, which are here provided in two profiles 93, 94, exemplary pieces forming longitudinal support parts for supporting a protective body provided with a fastening system 18.

[0083] More generally, the frame 15 typically comprises abutment surfaces distributed among two longitudinal support parts, all or part of the positioning member PM connects the peripheral margin 80 to the frame 15, and the frame 15 is - a protective body part 12, 112, 212; - a pouch 2 sandwiched between two plates 12A, 12B; It is understood that the purpose of the initiative is to sustain and support the

[0084] Some or all of the positioning members PM may constitute sliders, slidably mounted on or in the two longitudinal support parts and movable along a direction transverse to a longitudinal axis X1 (see FIG. 3 showing the axis of the protective body part, which axis may be merged with the longitudinal axis A of the pouch 2) between a first position and a second position: in a first position, in the unfilled state of the pouch 2, the slider is pushed outwards by the protective body part 12, 112, 212 (when it has its flat rectangular shape with a maximum perimeter) or is kept away from the abutment surfaces BS1, BS2, so that the slider can be further displaced inwards; In the second position, in the filled state of the pouch 2, the slider is engaged against one of the abutment surfaces BS1, BS2 respectively.

[0085] In some options, the positioning member PM can form a guide part for receiving one or more body cross members (screws, etc.). With reference to FIG. 10A, an insert piece IP can be provided in the positioning member PM, which piece IP is, for example, a rod-like cross member cooperating with a locking part, a nut or a bolt. Naturally, slots can be provided in the protective body part 12, 112 or 212 for the body cross member or any insert piece IP to cross the peripheral margin 80 in several places, thus stabilizing the positioning member PM (which in this kind of embodiment remains integral with the peripheral margin 80 when assembled). However, in a preferred option, the positioning member PM can simply clamp the margin parts 8a, 8 with a discontinuous distribution, while being in a state where they cannot be disassembled once they are introduced into the frame 15, typically inside the profiles 91, 92, 93, 94. Thus, there is no need for an insert piece IP and the margin portions 8a, 8b may be provided with boss portions B12, B12' or similar embossments for engaging with corresponding cavities in the positioning member PM.

[0086] Pouch characteristics and access for filling or emptying the pouch 3-4 and 10A-10B, 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 and joined together at four peripheral edges to provide a containment volume (internal volume Q) between sheets 21, 22, which are spaced apart by a predetermined distance in the filled state. One or more openings or ports 24 can be provided (e.g., formed as closable tubes between opposing parts of the peripheral edges of the sheets) to allow the pouch 2 to be filled or emptied.

[0087] In the illustrated embodiment, the protective body portion 12, 112 preferably has an attachment system 18 for fastening the two plates 12A, 12B such that, in the assembled state of the two plates, the protective body portion 12, 112, 212 includes a peripheral margin 80 extending annularly in the protective body portion reference plane P.

[0088] 3 and 4, among others, the peripheral margin 80 may be provided with at least one opening 80a capable of receiving at least one port 24 (e.g., two ports 24) of the flexible pouch 2. The protective body portion 12, 112 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 in the assembled state of the protective body part 12, 112, 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 can project axially outward from the second end side 120b. This arrangement with opening 80a can be provided in any other version of the protective body to accommodate a flexible pouch 2 having one or more ports 24 (with flexible hoses).

[0089] The tubes T may be associated with ports 24, where each of the tubes T is connected to a flexible pouch 2 by a port 24. Two forward ports 24 may be provided, for example, one port 24 forming an inlet for the flexible pouch 2 and the other port 24 forming an outlet for the flexible pouch 2.

[0090] 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.

[0091] 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 exclusively from thermoplastic materials (including, for example, polyethylene).

[0092] Tubing Holder 4, the plates 12A, 12B of the protective body optionally include an assembly 22 for holding two tubes T associated with two ports 24. The two plates 12A, 12B include, at their peripheral sides, complementary parts (e.g., complementary shapes along the Z direction) that form the assembly 22 for holding the tubes T.

[0093] The assemblies 22 for holding the two tubes 16 are arranged symmetrically with respect to the longitudinal direction X (i.e. the pouch longitudinal axis A which typically coincides with the axis X1). Each symmetrical part can hold one tube T or hose.

[0094] In another option, particularly suitable for accommodating higher volume pouches (e.g., between 30 or 50 liters and 200 liters), the frame 15 can directly support at least one bracket or similar retaining member for holding the tube T, as shown in Figures 7-8.

[0095] 6-8, one or two hoses or tubes T are typically connected to the front edge of the flexible pouch 2. The rear edge of the flexible pouch 2 can extend substantially parallel to the front edge at its opposite longitudinal end. Each tube T can be curved 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.

[0096] 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.

[0097] 6-8, one or more of the elongate 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 (formed by 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.

[0098] 6A and 10, the fastening means MF1, MF2 can comprise at least one fastening element, 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 is a bracket partially surrounding a receiving profile, which can be one of the longitudinal profiles 93, 94 or another profile 91, 92. Some holes in the profile can receive pins or similar retaining inner protruding parts of the bracket, for example for an anti-sliding effect.

[0099] The bracket may be elastically deformable, for example allowing removal of the fastening element to the frame 15, by moving the arms of the bracket further apart. Thus, the tubing holder formed by the fastening means MF1, MF2 may be removed once the line is no longer in use (the inlet line is no longer useful after the filling line has been disconnected).

[0100] 7 or 8, the tube T can be a filling line that is connected in a removable manner to the pouch 2 for the purpose of the filling operation. For example, the tube T, which is received and held / positioned by the fixing means MF1, MF2, is attached to the pouch 2 via a connector that forms a quick seal connector.

[0101] 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.

[0102] 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.

[0103] 6 to 8 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 protection device 10. A sliding structure can be used so that the protected pouches (in the frozen state) are carried by an annular frame or similar holding means which can extend vertically for storage purposes.

[0104] Protective body With reference to Figures 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.

[0105] The protective body 12 comprises two substantially planar plates 12A, 12B, each made from a single thermoformed plastic piece. The planar plates 12A, 12B also extend in a plane parallel to a main plane XY (here parallel to a protective body reference plane P). The plate 12A forms a lower surface S' and the plate 12B forms an upper surface S, with respect to a vertical axis Z. In a preferred embodiment, the two plates 12A, 12B are identical and symmetrically face each other with respect to the main plane XY.

[0106] The protective body is a thin body, while the plates 12A, 12B can be compared to a sheet with a relatively low flexibility, and the plates are made of the same material. The thickness e of each plate 12A, 12B is lower than the minimum thickness of the positioning member PM. The plates 12A, 12B can have a general curvature, but cannot be easily folded (the flexibility is substantially as low as that of PET).

[0107] Although the illustrated embodiment shows the protective body part 12, 112, 212 completely covering the two main walls W1, W2 by the covering part 8, other sizes can also be used for the covering part 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 the pouch edge 2A, 2B. 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.

[0108] With reference to Figures 1 and 4, the protective body part 12 is also provided with a mounting system 18 for fixing the two plates 12A, 12B to each other. In Figure 1, boss parts B12, B12' are provided for the plates 12A, 12B to be fixed to each other in a removable manner, the boss parts forming an interlocking form together with the outer projection of the first boss part B12, which defines the boundary of the hollow part, and the second boss part B12' being received in the hollow part by plastic retaining contact. Here, the second boss part B12' is a projection (preferably a hollow projection) projecting inwardly from the corresponding plate 12A or 12B. More generally, the plates 12A, 12B can be removably fixed to each other by the mounting system 18. Such a system 18 can also be of the type that can be seen specifically (schematically illustrated) in Figures 2A-2B and 3.

[0109] Optionally, the mounting system 18 can include a plurality of snap buttons 20A, 20B. One of the two plates 12A, 12B includes a first element 20A of a snap button, and the other plate includes a second complementary element 20B of a snap button. The second element 20B (possibly a male element) engages with the first element 20A (possibly a female element) in a direction parallel to the vertical axis Z. An insert piece IP (for example comprising a screw or a bolt) can also be used by crossing the peripheral margin at a particular hole or slot S80 (see FIG. 2B).

[0110] Alternatively, the attachment system 18 is a non-removable system, meaning 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. Clips can be used for such a non-removable fixation.

[0111] In the non-limiting embodiment of Figures 2A-2B and 4, the protective body part 12 includes snap buttons on the transverse sides 120a, 120b and on the two marginal parts 8a, 8b (typically between the covering part 8 and the longitudinal sides 121, 122). More generally, each of the two plates 12A, 12B is provided with a complementary member. Typically, the two opposite marginal parts 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 least in the two marginal parts 8a, 8b of the peripheral margin 80.

[0112] As can be seen in Figures 5 and 8, 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 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, with the typical difference that ribs can be provided on the outer surfaces of the plates 12A, 12B.

[0113] Exemplary Ribbed Pattern In each plate 12A, 12B, a group of ribs is provided with ribs R1, R2, R2', 800 that are located close to the peripheral margin 80. An optional other group of ribs may be provided with ribs R3, R4, 83, 84, 85, 86 that are located at a greater distance from the peripheral margin 80. Such ribs R3, R4, 83, 84, 85, 86 (which may be considered as a first group of ribs) may surround one or two panel portions PP, PP1, PP2, which typically form a rectangular panel, on the respective outer surface S, S' of the protective body part 12, 112.

[0114] Referring to FIG. 1, the plates 12A, 12B may each have a panel portion PP. For example, the panel portion PP may include: - a rib near the front side (front rib) provided with openings for one or more ports 24; - A rib (rear rib) located on the opposite side to the front side It extends between.

[0115] Each panel part can be strictly planar before assembly, except for some local projections (here, two projections 12p) that may possibly protrude in the same direction (outward) as the ribs. The projections 12p can be used to support temperature sensors. These projections 12p can be central projections, which are intersected by a central plane of the protective body part 12 that extends along the Z direction parallel to the width of the protective body part 12. The projections 12p can be arranged behind any one of the front ribs and in front of any one of the rear ribs.

[0116] More generally, the ribs may be distributed in groups, a first group having ribs R3, R4, 83, 84, 85, 86 which typically extend annularly (possibly having a square or rectangular shape with curved corners) in the peripheral annular region 8p of the covering part 8, since they are outside any panel part PP or PP1, PP2, while a second group of ribs having ribs R1, R2, R2', 800 which extend parallel to the first group of ribs and are arranged closer to the peripheral margin 80 compared to the first group.

[0117] Here, it can be seen that several transverse rib portions may be provided, which separate a short marginal portion of the peripheral margin 80 from one of the panel parts (panel PP1 or PP2). Thus, at least six or eight transverse ribs may be provided and distributed on the two opposite ends of each plate 12A or 12B. With reference to FIG. 5B, it can be seen that the groove G′ (and likewise its transverse groove portions) surrounding the panel PP1 or PP2 may be narrower than the groove G bounded by the side ribs R1 and / or 82. They may typically be narrower and less deep than the groove G or its transverse portions bounded by the transverse rib portions RP1, RP2.

[0118] 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.

[0119] 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.

[0120] 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. Fastening members 146, 147, 148 may be provided on one of these surfaces S, S' near an end side selected from the first end side 120a and the second end side 120b.

[0121] At least one of the lower surface S' and the upper surface S can be a surface with a plurality of ribs distributed in two longitudinally opposite parts of the surface, preferably including 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.

[0122] More generally, such transverse rib portions 4, 6 or RP1, RP2 provide an accordion effect due to the width of the corresponding grooves G1, G2 formed by the ribs and / or the height of the ribs (depth of the grooves G1, G2). This promotes local expansion of the plates 12A, 12B despite the planar structure of the peripheral margin 80 forming the protective body reference plane P. Typically, in the corner regions CR, the first and second transverse rib portions 4, 6 have heights that decrease as the space from the corner apex of the plate having such rib portions 4, 6 decreases. Thus, excessive expansion that may generate undesirable folding (along the diagonal) can be limited or prevented when having a height reduction for the corner rib portions extending into the corner regions 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 first and second transverse rib portions 4, 6 to promote spreading of fluid toward the margins 80 and toward the corners of the protective body portions 12, 112 when filling a flexible pouch 2 sandwiched between the plates 12A, 12B.

[0123] To have or improve abdominal retention effect, this is of interest. 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.

[0124] Some detailed embodiments of the protective body part 12 or 112 provided with a ribbed pattern will be described hereinafter.

[0125] 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 two grooves G2, each of annular shape on the plate inner surface.

[0126] 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.

[0127] 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.

[0128] It can also be seen that the ribs can be provided with height differences, such that they are more or less protruding outwards. For example, the transverse rib portions 4, 6 included in the annular or U-shaped ribs R1, R2, R2', 800 can be of increasing height (maximum height) with decreasing distance to the peripheral margin 80. Typically, ribs very close to the peripheral margin 80 can have a gradual rounding (having a larger radius of curvature) in their profile when viewed in cross section of the rib. Such ribs close to the peripheral margin 80 can also prevent waves or radial folds along an angled / diagonal direction from being generated in the plates 12A, 12B.

[0129] Such rib heights can be relatively large near the junction with the peripheral margin (thus allowing a greater slope effect locally), so that other ribs of lower height (possibly more rigid) can be provided around the panels PP, PP1 or PP2, with extensions of the plates 12A, 12B remaining substantially parallel to the protective body reference plane P.

[0130] Moreover, since the pair of U-shaped ribs R2, R2' are separated, as is the optional rib 800 (also U-shaped), there are no additional ribs in the intermediate region MR at equal distances from the front and rear ends E1, E2. It is preferred here to avoid multiple longitudinal ribs in the intermediate / edge portions of the protective body part 12, because having too many or too large / prominent ribs may negate the benefit of the belt effect created by the stopper 41 as shown in FIG. 12 (the belt effect is explained in more detail below). If present, such longitudinal ribs would then allow the expansion of the protective body part 12 in its center (bulging effect as in FIG. 6).

[0131] With reference to FIG. 8, in the final stage of filling, when 60% or 70% or more of the full capacity has been reached, the expansion of each plate 12A, 12B can be obtained with the slope being as reduced as possible in each panel (here in panels PP1 and PP2) if a belt effect is created. When the liquid pushing force becomes relatively large, there is a lateral expansion due to the accordion effect in the longitudinal rib portion 110 and in the transverse rib portions 4, 6, RP1, RP2. Such an accordion effect promotes the circulation of the liquid towards the edges instead of accumulating in the middle region M. The transverse rib portion 114 along the middle section MS also participates in preventing the liquid from accumulating only in the middle region.

[0132] In the corner regions CR, the height can be significantly lower than that of the transverse rib portions 4, 6 formed by the ribs R1, R2, R2', 800, which can be of interest in order not to compromise the integrity of the plate. Moreover, having a lower height in the ribs here can make it possible to have a transition as smooth as possible between the elongated sloped portion SP formed along the long side of the peripheral margin 80 and the elongated transverse sloped portion SP' formed along the short side of the peripheral margin 80.

[0133] It can also be seen that when the pouch 2 is filled, the ribs are provided in the thin areas of the protective body such that these ribs R1, R2, R2', 800 extend perpendicular to the slope, considered along the Z direction. With such an orientation, the parallel ribs are able to expand in an accordion fashion, with the provision that the pouch 2 is filled to a sufficient level (e.g., filled to more than 60% or 70% of full capacity) since the contents should provide enough internal pressure to push the ribs from the inside.

[0134] 14A, it can be seen that the rib pattern is of interest to guide the liquid (biopharmaceutical composition Q) towards the corners, at least when the internal pressure is sufficient to slightly deform the grooves G1, G2 bounded by the ribs R1, R2, R2'. In this exemplary embodiment, the wavy profile formed by the (accordion-like) ribs R1, R2, R2', R3, R4 is present near / on the edges of the covering part 8, such that the plates 12A, 12B can be stretched in these areas under the pressure of pouch filling: - a) when the pouch 2 (here of approximately 100 litre capacity) is filled to 60 litres, nothing in particular happens in the peripheral annular region 8p of the cover part 8 (see the top of Fig. 14A) since the pressure is still insufficient to deform the ribs; - b) As the pouch is filled to 75L the accordion like arrangement of ribs R1, R2, R2', R3, R4 will stretch under the pressure of pouch filling and plate 12A will stretch further at its centre if the belt effect is not provided.

[0135] It therefore shows that the arrangement of the ribs is of interest to delay / relatively reduce the increase in elongation, which causes higher filling in the panel part PP and lower filling on the outside of the panel part PP.

[0136] With reference to FIG. 14B, the rib profile for a high level of filling (which can be similar along the XZ or YZ plane) is also shown, where the pouch 2 is filled by at least 75L. If the edges of the middle parts of the marginal parts 8a, 8b are narrowed or provided with early stops 41 to limit the shrinkage (belt effect), the accordion arrangement of the ribs R1, R2, R2', R3, R4 of the protective body part 12 (for example, as in the embodiment of FIG. 3, and similar ribbed patterns) will stretch under the filling pressure of the pouch 2, and the panel parts of the protective body part 12 will remain flatter, since each panel part will be longer (along the Y direction towards the marginal parts 8a, 8b and along the X direction towards the ends E1, E2), thus minimizing the size along the Z direction in the middle part of each plate 12A or 12B.

[0137] The ribs R1, R2, R2', R3, R4 may each be bounded by a straight edge to define a respective imaginary rectangle. Moreover, the ribs R1, R2, R2', R3, R4 may extend around the panel part PP of the plate 12A, 12B, such panel part PP having a transverse dimension TL, which is equal to or exceeds half the width T12 (transverse dimension) of the plate 12A, 12B, as shown, for example, in FIG. 2B. The same is true for the embodiment with the ribs 110, 83, 84, 85, 86 typically disposed around the panel part PP1 or PP2, such that the respective panel part PP1 or PP2 has a transverse dimension TL, which is equal to or exceeds half the width T12 (see, for example, FIG. 5C).

[0138] Here, the length LL (longitudinal size) of the panel PP is also much larger than half the total length of the plates 12A, 12B. When having two panels PP1, PP2, the cumulative longitudinal size of the two panels PP1, PP2 can also be greater than or equal to the total length of the plates 12A, 12B. More generally, it is of interest to have a cumulative panel length that exceeds half the plate length.

[0139] Still referring to Fig. 14A, it is understood that the cross-sectional view from which such a profile is taken can correspond to a plane parallel to the YZ direction (preferably away from the mid-section MS). In the mid-section MS, the number of longitudinal rib portions (along the X direction) can be minimized due to clearance areas so as not to interfere with the belt effect. In some options (less preferred), the plates 12A, 12B can clamp the pouch 2 without the belt effect, for example when the pouch 2 does not need to be filled to its full capacity.

[0140] In some embodiments, all or part of the longitudinal rib portions are removed and only the transverse rib portions 4, 6, RP1, RP2 are present in at least one of the plates 12A, 12B. These transverse rib portions 4, 6, RP1, RP2 are already effective in allowing more liquid to be stored at the two opposite ends adjacent to the short margin portions of the peripheral margin 80. The more liquid can be stored near the corners and short sides, the lower the thickness of the protective body portion 12, 112.

[0141] The table below shows the effect of the size along the Z direction when using several ribbed patterns in the plates 12A, 12B, each time with the same belt effect using the configuration of the positioning member PM as in Figure 11A or Figure 12. The sizes as shown below are / reflect the maximum thickness of the protective body part in the non-frozen state. In the frozen state, the abdomen size can increase by approximately 25%.

[0142] [Table 1]

[0143] It can be seen that the U-shaped ribs (here ribs R2, R2' and R3, R4) are particularly efficient at the end of filling, when the pouch 2 clamped by the plates 12A, 12B is filled more than 75%. For this reason, a minimum size along the Z direction is obtained by this ribbed pattern. In a similar embodiment, fewer U-shaped rib sections can be used, for example as illustrated in Figs. 11A-11C. It is understood that if compactness with a size of less than 220 mm is desired for compaction, the pouch filling level will be too low (for example only about 55 liters for a 100 L pouch) without any suitable rib pattern to help in having liquid near the edge (i.e. near the clamp area). In contrast, the protective body part 12 with ribs R1, R2, R2' and R3, R4 is typically suitable for storing at least 88 liters or 90 liters for a 100 L pouch before freezing.

[0144] For situations where the pouch is filled to a lower level (e.g., about 70% or 75% or less), ribs as shown in FIG. 3 are more efficient in limiting the bulging effect in the intermediate region MR. For maximum filling, the ribs of this embodiment do not add much value, since it is the belt effect that first limits the total bulging size to less than 300 mm. In practice, 75% filling may be considered sufficient, since further expansion due to freezing is typically expected.

[0145] When analyzing the bulge effect as shown for example in Fig. 6, it can be seen that for the sloped parts adjacent to the peripheral margin 80, a relatively low angle is obtained. Indeed, these parts are near the mounting system 18 and therefore close to the clamping area. Here, it is observed that the protective body plates are more difficult to be deflected from the planar reference P at / near the edges, as if they were more rigid, because such peripheral areas are close to the clamping area (shorter lever arms).

[0146] Even if the pouch 2 is filled to only 75% of its full capacity, the mass of the biopharmaceutical product is concentrated in the middle of the covering part 8. Here, the plates of the protective body part 212 are not submitted to any belt effect on the one hand, and on the other hand, there is no rib pattern, which helps to have a narrower sloped part and / or a homogeneous slope (without interfering folds). The solution shown in Figure 7 or Figure 8 is of interest in order to have a better distribution of the biopharmaceutical composition Q over the entire lower surface S' of the protective body part 12, 112, such that the fluid is more present in the corner areas.

[0147] With reference to Figures 3, 5A-5D and 8, an example of a protective body part 112 having at least one plate 12A, 12B provided with two panels PP1, PP2 is shown. While the embodiment of Figures 1, 2A-2B shows a ribbed pattern (wherein the ribs can be considered as peripheral ribs arranged around the central panel portion PP of the plate 12A, 12B (all extending parallel to the peripheral margin 80, i.e. along the circumferential direction), Figures 3 and 8 show that several ribs or rib portions 114 can be provided in the intermediate region MR, possibly extending transversely to separate the two panels PP1, PP2 of the same plate 12A or 12B.

[0148] The rib portion 114 (forming the middle rib in this embodiment) may be suitable for obtaining a kind of "camelback" shape when the pouch 2 is filled. Several simulations have been performed to verify that this is efficient for limiting the total thickness of the protective body portion, for pouches filled with 75 or 100 liters of liquid biopharmaceutical composition Q. In practice, this pattern of ribs has a kind of molding effect, such that one obtains two small off-center abdomens, rather than a larger mass of product in the middle section MS.

[0149] Transverse rib portions RP1, RP2 may also be formed at the opposite ends of the cover parts 8, which are possibly interconnected to the longitudinal rib portion 110 by a smaller corner rib C1 provided in the corner region CR. In some options, the corner rib is not present. With reference to FIG. 5D, the intermediate portion 110a of the longitudinal rib portion 110 has here a minimum at a height H1' lower than the maximum height H1 of the longitudinal rib portion 110, which is found away from the intermediate region MR, where the belt effect can be implemented thanks to an early-stop positioning member PM specifically provided in the intermediate portion of the corresponding margin portions 8a, 8b. The difference H1-H1' can be at least equal to 2 mm or 3 mm.

[0150] 5A, the corner regions CR can be provided with less relief, where the maximum height H2 in the corner regions CR can be equal to or less than half the height H1 obtained in the longitudinal rib portion 110 of the outermost side rib R1 and / or in the transverse rib portion. By such an arrangement, possible fold lines are limited and are generated only in the corner regions CR along the diagonals DL1, DL2, thus corresponding to the "desired" fold lines, i.e. not interfering with the extension of the panel parts parallel to the protective body reference plane P.

[0151] In the illustrated embodiment, each of the two imaginary diagonals DL1, DL2 can intersect with a first series of corner ribs proximal to the first end side E1 and with a second series of corner ribs proximal to the second end side E2 and projecting outward. Each of the corner ribs is curved and connects two rib portions that are perpendicular to each other. Typically, the first transverse rib portion 4 is directly connected to the first series of corner ribs, while the second transverse rib portion 6 is directly connected to the second series of corner ribs.

[0152] Moreover, the first transverse rib portion 4 and the second transverse rib portion 6 may belong to an intermediate region between two corner regions CR extending perpendicular to the longitudinal axis X1 and respectively adjacent to the intersection of two of the four sides. Preferably, each corner region is more elastically deformable than such intermediate region provided with a transverse rib portion. Typically, each corner region is more deformable than any one of the side regions provided with a longitudinal rib portion 110.

[0153] Symmetrical rib patterns may be preferred. For example, the ribs on the lower surface S' are distributed in the two halves of the plate forming the lower surface S' and / or the rib pattern on the upper surface S is distributed in the two halves of the plate forming the upper surface S. According to the illustrated drawing, the same ribbed pattern is provided in the two complementary plates 12A, 12B, but in variants some differences may be provided. Optionally, one of the plates can be deprived of ribs.

[0154] The plates 12A, 12B form a reinforcing layer when they overlap (and preferably completely cover) the main walls W1, W2, respectively. The thickness e of each plate 12A, 12B before thermoforming may be about 1.27 mm, and therefore may be lower 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 3 The 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). The plate material may have a tensile strength at break between 45 MPa and 60 MPa, and may have a Young's modulus comprised between 1250 MPa and 1550 MPa along both the transverse direction (TD) and the machine direction (MD).

[0155] Shrinkage Management 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 in the pouch plane is reduced due to the inward movement of the different sides (also known as the retraction stroke). Now, in a horizontal configuration of the system 1 as illustrated in Figures 6-9, the four pouch sides can be displaced inwards due to vertical expansion (along the Z-axis).

[0156] The retaining and sustaining assembly HR can include a rectangular frame 15 or at least two longitudinal covering parts 31, 32, which are arranged to maintain the two longitudinal marginal portions of the peripheral margin 80 and allow the two plates 112A, 112B to move, expand and contract in a transverse direction belonging to the protective body reference plane P. 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 profile having a C-shape to define one of the internal cavities CP.

[0157] Now, with reference to Figures 9, 10A-10B, 11A, 11B, 11C and 12, an exemplary embodiment will be described for forming the positioning member PM as a stopper to prevent too great an inward displacement of some areas of the peripheral margin 80 as the pouch 2 becomes increasingly filled.

[0158] The positioning member PM may be adapted to cover the boss portions B12, B12' (such as those illustrated in FIG. 1) or similar embossments. For example, the positioning member may include several cavities each accommodating a respective pair of boss portions B12, B12'. With such an arrangement, there is no need for apertures or through holes in the margin portions 8a, 8b of the plate (only one hole may be provided for at least one port 24 at the front end of the protective body portion).

[0159] Typically, the frame 15 can accommodate the marginal portions 8a, 8b that are sandwiched by a plurality of discontinuous positioning members PM. Along the Z direction (see FIG. 1), the depth of each hollow bounded by the boss portion B12 or B12' (such depth defining the stroke for disengagement between the complementary boss portions B12 and B12') can be greater than the maximum spacing (measured along the Z direction) between the frame 15 and any one of the positioning members PM. In such an option, the frame 15 thus extends above and below each of the positioning members PM, preventing disassembly of each pair of boss portions B12, B12'.

[0160] Here, the frame 15 is provided with abutment surfaces BS1, BS2 or rims contained in the abutment members. Each abutment member can delimit an inner access to the housing, into which the positioning member PM extends. Typically, each profile 91, 92, 93, 94 forming a side of the frame 15 can be provided with an open end suitable for introducing a respective side (chosen from among the four sides) of the protective body part 12, 112, 212 inside the housing. The inner open side of the frame 15 is not used for the assembly or disassembly steps due to the presence of the abutment members, which prevent the possibility of the positioning member PM being inserted inside the profile 91, 92, 93, 94 or extracted outside the profile 91, 92, 93, 94 through the inner open side. In fact, on the inner side of each profile 91, 92, 93, 94 there is at least one abutment member BS1, BS2 extending transversely to the protective body reference plane P. Here, each profile 91, 92, 93, 94 has a C-shaped section, with an inner open side opening delimited between two vertically spaced abutment members. Each abutment member is here a continuous member elongated along the length of the corresponding profile. However, in variants, the abutment member can be divided into separate abutment regions or constructed in any suitable manner without interfering with the protective body reference plane P.

[0161] 11A and 11B, the positioning members PM are inserted by sliding insertion along a direction parallel to the long sides of the profiles 91, 92, 93 or 94 in which they are housed. The positioning members PM are thus inserted behind the abutment members and can remain behind the abutment members (forming the surfaces BS1, BS2) in the assembled configuration of the frame 15 around the protective body parts 12, 112, 212.

[0162] 11A-11C, each longitudinal support part (typically under the form of a profile 93, 94 or similar piece) defines one or more housings and is assembled with at least one adjacent support part (e.g. two transverse support parts) (also under the form of a profile 91, 92) (possibly). In some cases, an annular housing may be included in the frame 15 when the profiles 91, 92, 93, 94 are assembled, using a lower foot 115 and / or an upper foot 116 for supporting another frame 15. For example, the two profiles 93, 94 define a first housing and a second housing, respectively, in which the slider is mounted.

[0163] Here, the slider is - a first slider fitted into at least one cavity CP bounded by the first housing; and - a second slider fitted into at least one cavity CP defined by the second housing; and It can be seen that it is possible to include

[0164] 9, 11A and 12, it can be seen that the sliders in the first and second housings will act as stops, more specifically either as early stops 41 when mounted in an inwardly shifted manner on the peripheral margin 80, or as later stops 41', 42 which engage abutment members of surfaces BS1, BS2 at a later stage during filling of the pouch 2. The front surface BS of the early stop may already be engaged on one or more of the abutment members or rim portions provided on the frame 15 (here in the intermediate region MR) for the unfilled state of the pouch 2.

[0165] 11A, each transverse support part (here formed as a profile 91 or 92) is configured to receive an additional slider, at least part of which acts as an early stop, the front surface BS' of which (oriented towards the pouch 2) may possibly already be engaged on one or more of the abutment surfaces provided in the frame 15 (here in the transverse profiles 91, 92 or similar transverse support parts of the frame 15) for the unfilled state of the pouch 2.

[0166] In the illustrated embodiment, all or part of the positioning member PM is configured to slide, thus forming a slider that can be displaced inwards with an increase in the filling level of the pouch 2, as illustrated in Figs. 10A-10B. For a filling lever of more than 70% or 75% for the pouch 2, the angle α of the slope defined by the surfaces S and S' with respect to the reference plane P can be constant along the long sides, and possibly higher, in order to provide an accordion effect, when having ribs 110 whose height is greater than the plate thickness. Preferably, the maximum height H1 of the plate ribs can be greater than 3 mm with a rounded profile, such height preferably being less than or equal to the groove width (the groove width being the width of the hollow separating the two internal edges of the corresponding rib). Here, such ribs 110 extend in the longitudinal direction.

[0167] Typically, the width of each groove G1, G2, G can be greater than 10 mm or 12 mm, and preferably less than or equal to 35 mm or 40 mm. In an embodiment, either the ribs formed along the X or Y direction can have a width greater than 10 mm or 12 mm, while forming an elongated hollow / groove with an internal width of at least 10 mm.

[0168] 11A, 11B and 11C, a first group of positioning members PM is distributed longitudinally on the long side of the frame, while a second group of positioning members PM is located along the transverse area of ​​the peripheral margin 80 and distributed on the short side of the frame. When the members PM (which typically form sliders housed in profiles 91, 92) are mounted on transverse profiles or similar support parts, they are respectively slidably mounted and able to move along the direction of the longitudinal axis X1.

[0169] The frame 15 here has a rectangular shape thanks to the two longitudinal support parts and the transverse support parts, and it is therefore understood that the frame 15 can comprise abutment surfaces BS1, BS2, which are contained and distributed in the two longitudinal support parts and in at least one of the transverse support parts.

[0170] The positioning member PM (forming a slider within a frame 15, assembled for example as shown in Figures 11A-11C) is suitable to allow shrinkage management whilst using a hard material (aluminum) compatible with low / negative temperatures.

[0171] Details of an Exemplary Embodiment for Controlling Pouch Expansion In the embodiment of Figures 7-8, the plate dimensional reduction (when considered in the XY plane) can be obtained by the profile of the retraction stroke, such reduction being adjusted differently depending on the longitudinal position of several positioning members PM which locally prevent or limit such dimensional reduction in order to control the retraction stroke.

[0172] Here, the positioning members PM (which are fixed to the peripheral margin 80 as shown in Figures 9 and 10A-10B) 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.

[0173] All or part of the positioning member PM are stops for providing stroke limits between the stops 41, 41', 42 and the abutment surfaces BS1, BS2 contained in the frame 15 of the holding and sustaining assembly HR. With reference to Figure 12, the stops 41, 41' located at or near the mid-section MS of the pouch 2 are involved in creating a belt effect. In some embodiments, such a belt effect separates the two abdomens or bulges B1, B2.

[0174] The positioning members can act as stops 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 between, since a stroke is permitted in the area closer to the corner area CR (here in the end part 81).

[0175] Moreover, the optional ribs R1, R2, R2', R3, R4 prevent the plate outer surfaces S, S' 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 to expand the protective body portion 12, 112 from the inside without creating hollows or unsuitable fold lines that are detrimental to filling in the corner regions CR.

[0176] 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 will be longer than that of the intermediate parts, allowing to store at least the same liquid volume as in the absence of belly / bulging persistence.

[0177] Still referring to Fig. 12, 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. 12, such stops 41, 41', 42 follow the displacement (contraction) of the peripheral margin 80.

[0178] 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 since the abutment surfaces BS1, BS2 are aligned parallel to the X direction, these stops 41, 41' come into abutment against the abutment surfaces AB1, AB2 well before the stops 42 adjacent / facing the corresponding corner regions CR. A belly-lasting effect in the intermediate part of the protective body part 12, 112 is obtained.

[0179] In an option, ribs R1, R2, R2', R3, R4 are provided in the plates 12A, 12B. In such kind of option, the sustaining effect (a bulging effect decreasing in the intermediate region MR close to the center C) is completed by a regular expansion of the region around the panel PP or PP1, PP2, preventing the undesired formation of pronounced fold lines. In some cases, some corner ribs or rib portions C1, C2 have a height profile decreasing towards the intersection region with the diagonal line DL1, DL2.

[0180] Of course, Fig. 12 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.

[0181] One or more bulges / bellies B1, B2 as illustrated in Figures 13A-13B 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.

[0182] More generally, any configuration may be provided with a positioning member PM that can form a stop away from the corner region CR, so that a higher restraining effect can be obtained in the center of the pouch 2, as illustrated in particular in Figures 9A-9B. This is of interest for managing the freeze / thaw 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 6-9, 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.

[0183] The dashed lines in Fig. 13B 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 part 12, 112, 212, so as to limit the accumulated mass (of significant thickness) that may be difficult to unfreeze.

[0184] FIG. 13A 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 width of the pouch in the filled state as compared to the pouch width w in the empty state), and, - The length of the pouch 2 (L' < L, where L' is the length of the pouch in the filled state as compared to the pouch length L in the empty state).

[0185] In some variations, the positioning member PM can be positioned within the through slots and maintained in a stationary state, for example, by being fixed to or integral with a rigid frame 15 or a similar holding and sustaining assembly. The slots in the protective body portion can be of a larger size only near the end side portions 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 if the positioning member is an early stop member).

[0186] The holding and sustaining assembly HR can include at least three positioning members PM distributed at each of the longitudinal side portions 120c, 120d, and typically, one or two central stoppers 41 correspond to the positioning members PM arranged away from the corner region CR.

[0187] Referring to FIGS. 7 - 8, due to the lower flexibility of the materials of the two plates 12A, 12B, the pouch expansion is restricted and controlled by the protective body portions 12, 112. The protective body portions are 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 (trademark) type.

[0188] The flexible pouches 2 may be frozen, thawed, filled, or emptied simultaneously as they are stored on top of the stacked protective body portions 12, 112 using the frame 15. The biopharmaceutical fluid may be frozen or thawed as the flexible pouch 2 is stored. When the flexible pouch 2 is shipped, in most cases the biopharmaceutical fluid is thawed, even though it may be frozen as well.

[0189] 4, it can be seen that the two plates 12A, 12B can also include through-holes 25, for example regularly arranged on the peripheral sides of the two plates, which coincide in the assembled state of the protective body part 12 and extend in the marginal parts 8a, 8b, so as to form protective body part through-slots that do not interfere with the covering parts covering the pouch 2. More generally, a protective body part through-slot, any kind of relief or a suitable positioning member PM is provided in one or more of the marginal parts 8a, 8b, so as to cooperate with a complementary element adapted to limit the expansion by preventing or limiting the inward displacement of the longitudinal sides 120c, 120d of the protective body part in the assembled state. Such complementary elements form positioning members PM since they are involved in determining the final position of the longitudinal side sections at the end of filling of the flexible pouch 2 by abutting against the outer edges, typically contained within the margin portions 8a or 8b.

[0190] 4, the flexible pouch 2 typically includes a through hole 2c, here along one of the transverse sides, that can form a handle for the flexible pouch 2. This is of interest when the pouch volume is low enough to allow manual carriage of the pouch 2.

[0191] The plates 12A, 12B have here the same thickness e, as shown in Fig. 4, which is a constant thickness in the plate contact parts for contact with the pouch (which here form the covering part 8). Such a thickness e can also be present in the marginal parts 8a, 8b in the areas provided with through-slots. In some variants, the marginal parts 8a, 8b can be reinforced by at least one additional reinforcing layer.

[0192] The length of the two opposite marginal portions 8a, 8b is here substantially the same. Such a length can be, for example, more than 250 mm, or preferably more than 350 mm, which is of interest in order to provide at least three through-slots that are regularly distributed in at least one marginal portion (preferably in all of these marginal portions 8a, 8b) while having good robustness. This length can represent more than 75% of the total length of the pouch 2 before filling it.

[0193] The freeze / thaw system 1 may optionally be provided with clamps (here, two clamps 11, 13 in the example of FIG. 4). Each clamp 11, 13 is positioned near a corner between the front edge 2a and a long side or similar longitudinal edge of the flexible pouch 2. Each clamp 11, 13 clamps one hose or tube T at a straight angle. Thus, each plate 12A, 12B may include cutouts positioned at each corner between its front edge and an adjacent edge parallel to the longitudinal axis A. These cutouts generate free spaces that can be occupied by the clamps 11, 13.

[0194] Such an arrangement allows the frame or similar holding assembly HR to possibly support only the two marginal portions 8a, 8b. The frame structure can be particularly simple when the volume of the pouch 2 is below 10 or 20 liters.

[0195] Independently of the manner in which the positioning members PM are provided in the peripheral margin 80, the protective body portion 12, 112, 212 mounted to clamp the flexible pouch 2 may be received in a single cavity of the interior space of any suitable retention and retention device HR, which is rigid and defines the outer periphery 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 with a ribbed pattern.

[0196] To accommodate the corresponding thickness variations (as measured along the Z-axis direction from the protective body reference plane on the corresponding outer surface S or S'), the holding and sustaining device can be of annular shape that does not cover the covering part 8. Due to the expansion control and early stopping effect in the middle part 82, one or more bulges / bellies B, B1, B2 can be formed, making the middle section MS illustrated in FIG. 13A much less movable compared to the complementary section of the protective body 12. In the middle section MS, the total thickness (or maximum of the thickness) is less than 300 mm, for example approximately 230 mm or 260 mm, while the total length of the protective body is typically more than 1400 mm. In other words, the thickness:length ratio can be kept below 1:4, which is of interest for stack efficiency and compactness.

[0197] The system 1 is well adapted for freezing, storing and thawing biopharmaceutical materials stored in a simple concept flexible pouch 2. The protection device 10 as described above is of interest for filling the pouch 2 with controlled and limited expansion, such that the expansion is limited in one or more areas where the fluid thickness would reach a maximum if no expansion control were performed. 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. 13A.

[0198] 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, which are respectively formed in front of and behind the belt line BL (the line crossing the at least one recess). Naturally, such an effect does not prevent fluid communication between the two opposite regions where the bulges B1 or B2 are formed. This allows a generally equal distribution of the fluid. Since two or more regions are generated with bulge formation, a more uniform thickness distribution is obtained without reducing the volume of the pouch 2. In other words, the reduced thickness of the respective region reduces the thickness at any one point in the pouch 2, and therefore no "belly" is formed.

[0199] The rib pattern also promotes having a belting effect without undesirable waves or folds that would impair the filling in the corner regions CR.

[0200] The pouch 2 and storage unit 10 can be exposed to temperatures of about -70°C or less to freeze the biopharmaceutical fluid. The annular shape of the shell HR is of interest to provide a recessed area where cold 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 a retention and sustaining device for controlled expansion, so as to eliminate or reduce the formation of oversized protrusions during freezing. In some options with a shell covering / contacting the covering part 8, this also facilitates the separation of the shell HR halves or protective parts 3, 4.

[0201] 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.

[0202] 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 greater than wide, and 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 that includes two flat portions.

[0203] In the preferred embodiment as shown, the positioning members PM are sliding members which are inserted into slots or holes or through-slots 25 in the peripheral margin 80. In a variant, the protective body part through-slots may be replaced by at least one cavity or hollow contained in the respective plate for receiving a positioning member PM which prevents inward movement locally in the margin portion 8a or 8b.

[0204] The variation in clearance for the retraction stroke can be obtained by an abutment member contained in a shell or covering part which is differently positioned relative to the through hole portion 25, as in FIG. 4, the abutment member or positioning member PM being made separately from the device HR and mounted on the frame 15, with the stroke being limited by suitable surfaces BS1, BS2.

[0205] 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 defined by the appended claims, and therefore, it is intended that the invention be limited only by the following claims.

[0206] 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]

[0207] 1. Freeze / Thaw Containment System 2 Flexible pouch 2a Front edge 2c Through hole section 2r Reception Department 4 first transverse rib portion 6 Second transverse rib portion 8 Covered parts, covered parts 8a, 8b Plate margins 8p peripheral annular region 10 Protection devices, storage units 11 Clamp 12 Protective body 12A Lower Plate 12B Upper plate 12p protrusion 13 Clamp 15 Frames 17 Connector 18 Mounting systems, mounting devices 20A First element: snap button 20B Second complementary element, snap button 21 sheets 22 Assembly for holding sheet and tube 24 Ports 25 Through hole 31 Longitudinal covering parts 32 Longitudinal covering parts 41 Early Stopper 41', 42 late stopper 80 Periphery Margin 80a opening 81 End parts 82 Middle part, side ribs 83, 84, 85, 86 Ribs 91, 92, 93, 94 Profiles 110 Longitudinal rib section 110a middle part 112 Protective body part 112A, 112B Plates 114 Transverse rib section 115 Lower foot 116 Upper foot 120a first end side, transverse side 120b second end side, longitudinal rear side, transverse side 120c, 120d Longitudinal side 146, 147, 148 Fastening members 212 Protective body part 800 Ribs A Pouch Longitudinal Axis AB1, AB2 abutment surfaces B1, B2 bulge B12 First boss part B12' Second boss part BL Belt Line BM, BM' biasing member BS, BS' anterior surface BS1, BS2 Contact surface, contact member C center C1, C2, C1', C2' corner ribs CP Cavity CR Corner Area DL1, DL2 Virtual diagonal E1 Front end, first end side E2 Rear end, second end side e Thickness F9 side G, G', G1, G2 Groove GS Groove H1 Maximum height H1' Height HR Retention and Sustainment Assembly, Retention and Sustainment Device IP insert piece, insert piece J Periphery seal L Pouch length when empty L' Pouch length in filled state L8 Length LL Length of panel PP 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, panel parts PP1 Panel part, panel parts PP2 Panel parts Q Biopharmaceutical Composition R1 Rib, Side Rib R2, R2', R3, R4 Ribs RP1, RP2 Transverse rib section S Upper surface, outer surface, second surface S' lower surface, outer surface, first surface S80 Holes, slots SL Slide SP Long, narrow section with slope SP' Long, narrow transversely sloped section T Hose / Tube T12 Plate Width TL Transverse size UP Upper part w Pouch width when empty w' Pouch width in filled state W1, W2 Main walls W8 Maximum width of positioning member PM X-axis, longitudinal X1 Longitudinal axis XY principal plane Y axis Z vertical axis α Plate deflection angle

Claims

1. 1. A protective device for use in freezing, storing, and thawing a biopharmaceutical material contained within a flexible pouch, said protective device comprising: - 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, the plates being formed from a plastic forming plate material, the plate material being deformable but less flexible than a plastic material of the flexible pouch; - a mounting system for fastening said two plates, such that in an assembled state of said two plates, said protective body part includes a peripheral margin extending annularly in a protective body part reference plane, said peripheral margin being provided with at least one opening capable of receiving at least one port of said flexible pouch; Including, the two plates define two mutually unfixed opposing parts forming a covering part for covering the flexible pouch, the covering part being surrounded by the peripheral margin; 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, whereby the protective body portion is expandable from the planar state; The two plates are configured to clamp the flexible pouch to constrain the flexible pouch in a filled state of the flexible pouch, and the protective body part is deformable due to contraction of the two plates in at least one direction belonging to a protective body part reference plane; The two plates form first and second outer surfaces of the protective body part, facing in opposite directions, at least one of the first and second outer surfaces being: a number of ribs, which extend along the peripheral margin at least over a peripheral annular area of ​​the covering part and are intended to locally structure the covering part of the protective body; a wave-like profile resulting from the ribs defining elongated grooves in the corresponding inner plate surfaces, whereby the ribs serve to promote expansion in a direction transverse to the reference plane of the protective body; a surface having A protective device, wherein on at least one of the first outer surface and the second outer surface, the ribs provide an accordion effect.

2. 2. The protection device according to claim 1, wherein the plurality of ribs are distributed on at least two opposite parts of the surface, the opposite parts being longitudinally opposite.

3. 3. The protection device of claim 2, wherein the plurality of ribs includes one or more first transverse rib portions proximate or adjacent to the first end side and one or more second transverse rib portions proximate or adjacent to the second end side.

4. 4. The protection device of claim 3, wherein the plurality of ribs further includes a group of elongated rib portions extending in the peripheral annular region of the covering part perpendicular to any one of the first transverse rib portion and the second transverse rib portion.

5. 5. The protection device of claim 4, wherein the group of elongated rib portions includes two opposing elongated rib portions that are longer than any one of the first transverse rib portion and the second transverse rib portion.

6. 5. The protective device of claim 4, wherein the protective device includes a curved corner rib, the corner rib including a first corner rib interconnecting one of the elongated rib portions with one of the first transverse rib portions.

7. 7. The protective device of claim 6, wherein the corner ribs further include a second corner rib interconnecting one of the elongated rib portions with one of the second transverse rib portions.

8. a continuous rectangular area without ribs on said surface is surrounded by the first group of ribs and the second group of ribs; - the first group of ribs extend annularly in the peripheral annular region of the covering part, 5. A protection device as claimed in claim 4, wherein the second group of ribs extend parallel to the first group of ribs and are positioned closer to the peripheral margin compared to the first group.

9. 3. The protective device of claim 2, wherein the first outer surface bounded by the peripheral margin is a lower surface of the protective body portion, while the second outer surface bounded by the peripheral margin is an upper surface of the protective body portion.

10. the protective body portion is provided with ribs on the first outer surface and on the second outer surface; a first plurality of ribs defining corresponding grooves formed on the first outer surface; a second plurality of ribs defining corresponding grooves are formed on the second outer surface; The protective body is configured to expand along a direction perpendicular to a reference plane of the protective body due to filling of the flexible pouch sandwiched between the two plates, such that the two mutually unfixed opposing parts form respective panels, each of the panels comprising: - extending parallel to the protective body reference plane; 3. A protective device as claimed in claim 2, wherein the peripheral margin is surrounded by an elongated relief extending parallel to the peripheral margin, the relief being formed by a part of the rib which projects outwardly and is contained within the protective body.

11. the protective body portion is provided with ribs on the first outer surface and on the second outer surface; a first plurality of ribs defining corresponding grooves formed on the first outer surface; a second plurality of ribs defining corresponding grooves are formed on the second outer surface; 4. The protection device according to claim 3, wherein each of the two plates includes at least one plate panel part extending between the first transverse rib portion and the second transverse rib portion.

12. 2. The protective device according to claim 1, comprising a retaining and sustaining assembly for supporting the protective body part at the peripheral margin, away from any one of the ribs of the protective body part, the retaining and sustaining assembly comprising a frame with an abutment surface arranged between the covering part and the peripheral margin, adapted to allow the two plates to move, extend and contract in a transverse direction belonging to the protective body part reference plane without the peripheral margin being displaced inward beyond the abutment surface.

13. the plurality of ribs includes one or more first transverse rib portions proximate or adjacent the first end side and one or more second transverse rib portions proximate or adjacent the second end side; the peripheral margin is provided with a positioning member spaced from any one of the ribs of the protective body portion; 13. The protection device of claim 12, wherein the positioning member is configured to limit movement of at least one part of the peripheral margin in the transverse direction by abutment against the abutment surface, thereby limiting expansion of the flexible pouch in at least one region intermediate the first transverse rib portion and the second transverse rib portion.

14. 4. The protection device of claim 3, wherein each of the first and second transverse rib portions extends perpendicular to the longitudinal axis and belongs to an intermediate region between two corner regions adjacent to the intersection of two of the four sides, the two corner regions being formed so as to be more elastically deformable than the intermediate region provided with the first transverse rib portion and the intermediate region provided with the second transverse rib portion.

15. each intermediate region is adjacent one of the first end side and the second end side; each of the first outer surface and the second outer surface includes a longitudinal rib portion extending parallel to the longitudinal axis in two opposing side regions, each proximal to the peripheral margin and distal to the longitudinal axis; 14. The protection device of claim 13, wherein each of the corner regions is configured to be more elastically deformable than any one of the side regions provided with the longitudinal rib portion.

16. 2. The protective device of claim 1, wherein the two plates are two separate pieces having the same perimeter size and the same outer shape, and each of the first outer surface and the second outer surface includes a first transverse rib portion proximate the first end side and a second transverse rib portion proximate the second end side.

17. 10. The protective device of claim 1, wherein the plurality of ribs and the protective body portion are made from the same freeze-resistant polyester or copolyester material, and the two plates are two separate pieces.

18. 2. The protection device of claim 1, wherein each rib of the plurality of ribs defines an inwardly opening internal hollow portion that opens toward the flexible pouch, and each rib of the plurality of ribs is separate from the peripheral margin such that the internal hollow portion provides additional volume in a gap between the two plates.

19. The two plates have the same thickness, less than 2 mm, and each of the two plates has a density of 1.10 g / cm 3 13. The protection device of claim 1, having a density greater than 1.0 and made of a plastic material.

20. Each of the two plates is a plate having a rectangular shape with four corners and two imaginary diagonals, and the two imaginary diagonals intersect a pair of corner vertices of the four corners, respectively; each of said two imaginary diagonals intersects a first series of corner ribs and a second series of corner ribs; - the first series of corner ribs are proximal to the first end side and project outwardly along a direction perpendicular to the protective body reference plane; 2. The protective device of claim 1, wherein the second series of corner ribs are proximal to the second end side and protrude outwardly along a direction perpendicular to the protective body reference plane, each of the corner ribs being curved and connecting two rib portions that are perpendicular to each other.

21. 1. A freeze / thaw containment system for storing a biopharmaceutical composition, the freeze / thaw containment system comprising: A protection device according to claim 1; A flexible pouch sandwiched between two plates, said flexible pouch being fillable with a biopharmaceutical composition through at least one port in said flexible pouch projecting outwardly through at least one opening, said flexible pouch being more flexible than a material of a protective body portion. A freeze / thaw containment system.

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