Sealing device and method for detecting possible gas leaks from the assembly joints of a biopharmaceutical product

Abstract

The sealing arrangement comprises a connection device (1) and one or more housing parts (201) of a housing unit for enclosing a component, typically an attachment component (15) forming a head of the connection device. A gas permeable end formed in such a component (15) can be isolated so that the sealing arrangement is suitable for detecting a detectable gas in a detection chamber which is hermetically sealed. Due to a sealing structure (4) configured at the passage for fastening the connection device, a housing unit is obtained with a tight radial contact around the middle part of the connection device. The device (1) is fitted with a flexible hose end, preferably at a barbed nozzle (1a) formed at the end opposite the gas permeable end. By this arrangement, the hose installation can be tested with respect to its integrity.

Description

Technical Field

[0001] This invention relates to the field of connecting devices and similar accessories used in bag assemblies, which are provided as sterile components suitable for the circulation and / or supply of biopharmaceutical fluids. More specifically, this invention relates to a sealing arrangement for integrity testing of hose / tube connections involving connecting devices, typically performed by detecting detectable gases in a hermetically sealed test chamber.

[0002] The term "biopharmaceutical fluid" is understood to refer to products (culture media, cell cultures, buffer solutions, artificial nutrient solutions, blood products, and derivatives of blood products) or pharmaceutical products produced by biotechnology, or more generally, products intended for use in the medical field. Such products are in liquid, paste, or possibly powder form. This invention also applies to other products with similar requirements regarding their packaging. These products typically have high added value, and ensuring the integrity of the packaging containing such products (especially the absence of any contamination) is crucial.

[0003] For storage and transportation purposes, these biopharmaceutical fluids are typically housed in bags with flexible, sealed, and sterile walls made of plastic. Importantly, these bags must be leak-proof, or at least to a satisfactory degree, before or during use of the biopharmaceutical fluid, thus protecting their potential contents from any deteriorating factors (such as contamination) originating from outside the bag. Therefore, it is necessary to be able to easily detect any loss of bag integrity before, during, or after use. The same requirement applies to connections, particularly those at fittings, within a set of fittings, or provided in 2D or 3D bag manifolds. Background Technology

[0004] Bag assemblies for biopharmaceutical fluids comprise various components such as hoses, adapters, fittings or connectors, reducers, and filters. These assemblies are prone to leakage not only around seams and ports but also around tube / hose connections, particularly at hose barbs on components. Integrity testing of the bag assembly using helium or a similar tracer gas typically ensures the tightness of all connections. This helps eliminate the risk of filling defective single-use bags (otherwise, high-value biopharmaceutical contents could be altered and / or lost, rendering them unusable).

[0005] Leak testing of biopharmaceutical systems prior to use typically requires the creation of a chamber in which the system is placed within a test chamber. A pressure differential is then established between the internal chamber defined by the system (which may include hoses and one or more connectors) and the test chamber. A tracer gas is introduced into the higher-pressure chamber, and a connection is established between the lower-pressure chamber and a detection device (such as a mass spectrometer) sensitive to the tracer gas to detect any leaks of the tracer gas from the higher-pressure chamber to the lower-pressure chamber.

[0006] However, leaks between the connector and the tubing are not always observable. For example, many sterile connectors use a gas-permeable membrane as a sterile barrier, covering the open end of the connector opposite the barbed end. This gas-permeable barrier at the end of the tubing presents a challenge for integrity testing. In practice, the tubing must be clamped before the sterile connector, making it impossible to test the integrity of the connection around the tubing barbs on the connector, and leaving the component at risk of leakage or contamination.

[0007] When a part of the system cannot be tested within a vacuum chamber, a helium sniffing procedure can be performed manually. This may detect leaks. However, when performing leak tests, manual sniffing and helium injection are prone to operator variation. These exhibit high dispersion in measurements, thus reducing the sensitivity of the test method. Furthermore, performing such tests on complex products is often impractical.

[0008] Therefore, particularly in the specific field of this invention, there is a need to effectively test biopharmaceutical systems designed to be filled with biopharmaceutical fluids at fittings or connectors, while easily and reliably detecting the smallest possible micron-sized and possibly submicron-sized pores when testing the integrity of such connectors before use, and generally with a higher level of reliability than currently known or used manual methods. Summary of the Invention

[0009] To improve the situation, embodiments of the present invention provide a sealing arrangement comprising:

[0010] - A housing unit having a first housing portion, a second housing portion and an access channel, wherein the first housing portion and the second housing portion define the internal volume of the housing unit in a closed state, and the internal volume can be accessed through the access channel;

[0011] - A connecting device comprising a tubular portion extending from a first annular portion to a second annular portion, the tubular portion defining a fluid passage and having an intermediate portion of an annular shape arranged around the fluid passage between the first and second annular portions; and

[0012] - A sealing structure adapted to form an airtight joint near the channel by continuous contact around the middle portion when the second annular portion is contained in the internal volume in the closed state of the housing unit.

[0013] The first annular portion is configured to have overlapping ends of a flexible hose, while the second annular portion is provided with an attachment member.

[0014] The housing unit is configured to receive the attachment member within an internal volume such that at least one gas-permeable end included in the attachment member is enclosed within the internal volume, and gas escaping from the fluid passage via the at least one gas-permeable end is retained within the internal volume.

[0015] This solution is typically used to test detectable gases in a hermetically sealed test chamber to assess the integrity of the hose connection around the first annular portion of the connecting device (which may be a barbed nozzle). With this arrangement, the detectable gas (tracer gas, such as helium) used in the integrity test and flowing through the permeable end can be hermetically contained within the internal volume (without escaping outside the housing unit until the housing unit is opened), thus ensuring the integrity test is effective.

[0016] Here, in this application, "hermetically tight" is used in its usual understanding in the field of leak detection, namely: hermetically tight with a gas barrier effect. When the tracer gas is helium, a small fraction of this gas (which is very light) may escape from the hermetically tight housing / shell unit at a low rate without affecting the integrity test. Therefore, "hermetically tight" does not necessarily mean "permanently helium-sealed": on the contrary, such escape may occur at a low rate (typically over a long period of time) without causing any difficulty in detecting small leaks in the system under test.

[0017] Advantageously, this sealing arrangement provides a means for enabling components to undergo full integrity testing via open / sterile end connectors at the ends of their conduits. The housing unit can be reusable. The sealing structure can be at least partially reused, possibly for a limited number of different tests. Due to the sealing structure used as a peripheral seal and constructed at the passage for fastening the connection, a housing unit with tight radial contact around the middle portion of the connection is obtained.

[0018] The housing unit can be made of a simple housing that is easy to interlock and preferably easy to clamp. Such housings are designed in such a way that they can airtightly enclose the free end of a component such as a connector at the end opposite to the hose barb or similar male part for connecting to the hose.

[0019] This solution facilitates the easy implementation of tracer gas testing. Since the connection device is typically attached to a hose, the sealing arrangement is of interest so that:

[0020] - In the preparation phase, a fluid transfer assembly is formed, wherein the end of the flexible hose overlaps with the barbed nozzle or similar first part of the connecting device, and is optionally surrounded by a clamping collar; the housing unit is closed by applying a sealing structure at the interface between the housing parts and between the housing parts and the intermediate part of the connecting device;

[0021] - During the testing phase (using the detection chamber), tracer gas is allowed to be injected into an internal space that includes a fluid passage and an internal volume and is separated / isolated from the outside by a sealed contact area between housing parts completed by a sealing structure, and any escape of tracer gas toward the detection space of the detection chamber (due to possible defects) is detected by a tracer gas sensor device that is in fluid communication with the detection space.

[0022] The tracer gas (e.g., helium) injected into the fluid pathway can flow in an additional volume within the housing unit. This additional volume can be less than 25 or 30 cm³. 3 It may be less than 10 or 15 cm 3 .

[0023] In the closed state of the housing unit, the sealing structure uses two different sealing devices to clamp the intermediate portion, forming a sealing ring or similar annular portion around the intermediate portion. Optionally, the sealing structure consists of two sealing members, each defining a perimeter. This perimeter can be matched to the following perimeter shapes and dimensions:

[0024] - The perimeter of the first connecting edge included in the first housing portion

[0025] - The perimeter of the second connecting edge included in the second housing portion.

[0026] When the first and second connecting edges are joined together, a groove (around the internal volume) can be formed in the housing unit. A sealing structure can extend within this interface groove.

[0027] More generally, the sealing device forming the sealing structure is adapted to be fastened and sealed in the intermediate section around the neck of the connecting device or similar suitable segment. Typically, the second annular portion is enclosed without any contact with the internal end faces of the housing unit. More generally, it should be understood that fastening and loosening the housing or similar housing portion is a simple operation without any risk of damaging the first and second annular portions involved in the connection.

[0028] In embodiments, the sealing arrangement may include at least two housings and at least two sealing devices. The housings are housing portions designed such that they can airtightly (hermetically seal) the free ends of connecting devices that relate to forming a fluid connection at the end of a flexible hose / tube. The sealing devices may be divided into two halves, each half being removably attached to one of the two housings. Using the sealing devices, helium diffusion is sufficiently inhibited or prevented, thereby effectively allowing measures for leak testing to be performed outside the housing unit (e.g., in a detection chamber).

[0029] More generally, in an integrity test configuration, the sealing structure forms an airtight joint. This airtight joint prevents air from the surrounding housing unit from entering the internal volume and generally prevents any gas supplied to and reaching the internal volume via fluid passages from escaping from the internal volume.

[0030] The connecting device typically comprises a single component, which includes the first annular portion and the fluid passage. The connecting device can be a single plastic component. The housing unit can be made of two shells (preferably, in some alternatives, two halves of the same component). This structure simplifies the test preparation phase.

[0031] In some alternatives, the housing unit may be part of a multi-cavity assembly configured to define several internal volumes, each associated with a channel, and suitable for enclosing a permeable end of a connection device involved in forming a fluid connection opposite to the first annular portion. The permeable end may be provided with a preferably folded membrane.

[0032] The first annular portion of the assembly component may have a retaining portion, which includes at least one retaining outer annular edge or rib adapted to locally deform or increase the deformation of the flexible hose. Typically, the middle portion of the connecting device remains away from the flexible hose. The flexible hose in the engaged state has a contact portion or a tapered portion that is sandwiched between an outer collar (which may be a clamping collar or a crimping collar) and the retaining portion.

[0033] Typically, the first annular portion has a rigid connecting end that forms a male tubular end, which is adapted for insertion into the open connecting end of a flexible hose forming a female portion. Only the hose deforms, while the nozzle-shaped portion or insertion tubular portion of the second connector remains undeformed.

[0034] In various embodiments of the sealing arrangement, it is also possible to use one and / or another of the following details, either alone or in combination:

[0035] - When the housing unit is closed, fluid communication between the internal volume and the outside of the housing unit is possible only through a fluid passage.

[0036] - One of the first and second housing portions is attached (either in a fixed or removable manner) to the wall that defines the test chamber and belongs to the integrity testing equipment.

[0037] - The connection device is a single-use device (disposable because it cannot be reused after a single use in cases where a specific biopharmaceutical fluid flows through the fluid pathway).

[0038] -The first annular section is a hook-shaped nozzle made of plastic;

[0039] - The first annular portion is provided with at least one protrusion, and the first annular portion preferably includes at least one barb.

[0040] - The first annular portion is rigid and has a tapered portion that gradually tapers away from the middle portion;

[0041] - The cross-section of the first annular portion is smaller than the cross-section of the second annular portion;

[0042] - The at least one protrusion in the first annular portion includes an external protrusion, preferably adjacent to or close to the axial opening of the connecting device.

[0043] - The first annular portion is included in the same plastic part that includes the second annular portion.

[0044] - Plastic parts are rigid parts made of thermoplastic materials.

[0045] - The sealing structure includes at least one member sandwiched between a first rigid member forming all or part of a first housing portion and a second rigid member forming all or part of a second housing portion.

[0046] -The sealing structure is located at the junction between the first housing part and the second housing part.

[0047] -The sealed structure can be elastically deformed.

[0048] - The sealing arrangement also includes clamping members arranged at the periphery of the housing unit.

[0049] - The clamping member is adapted to maintain the compressed state of the sealed structure by locking the closed state of the housing unit.

[0050] - The clamping components can be arranged around the internal volume.

[0051] The two rigid members can be clamped together to compress the sealing structure made of deformable plastic material.

[0052] - The sealing structure includes two deformable elements, each made of a flexible plastic material.

[0053] The two deformable elements of the sealing structure include two basic planar portions (flat portions) that are parallel to each other and connected to each other in the closed state, and a ring that is complementary to the two basic planar portions.

[0054] -The ring surrounds and encloses the middle portion.

[0055] - The sealing structure is provided with rings distributed in the two deformable parts.

[0056] The connecting device can be a connector suitable for aseptic connection at an attachment member, which forms the head portion of the connecting device. The connecting device has an annular recess or neck, with a middle portion extending at such an annular recess or neck.

[0057] The connecting device can extend linearly, and the two opposite openings are centered on the same longitudinal axis.

[0058] In some embodiments, the at least one gas-permeable end included in the attachment member includes an end opening, the end opening being:

[0059] - Belongs to the second ring section; and

[0060] - Covered by a gas-permeable membrane.

[0061] Alternatively:

[0062] - The recess can be formed into a groove with a bottom line having an annular shape (preferably circular).

[0063] - The bottom line of the groove is covered by a ring of sealing structure.

[0064] - The first and second housing parts are made of or comprise metal materials.

[0065] - The two housing parts are two pieces.

[0066] -Optionally, the metal material can be stainless steel.

[0067] - Optionally, one or more rigid clamping members may extend in parallel holes (extending perpendicular to the plane portion of the sealing structure), the one or more rigid clamping members being used to close the housing unit and hold / lock the housing unit in a closed state.

[0068] In various embodiments, the sealing structure may include at least one of the following features:

[0069] - The sealing structure can be easily removed from the connector.

[0070] -The sealing structure extends around the middle portion by extending in the annular recess of the connecting device.

[0071] - The sealing structure has two stacked sealing members, each of which has a bridging portion (a rounded portion, preferably continuously curved).

[0072] - The parts of the sealing structure are preferably made of the same plastic material.

[0073] Optionally, the housing unit is provided with a connector fitting, preferably of metal, that defines a communication conduit outside the fluid passage that leads into the internal volume of the housing unit.

[0074] Connector accessories may be included in or integrally formed with a single-piece housing portion (typically forming a first or second housing portion).

[0075] Connector accessories may include check valves.

[0076] The housing unit may include a first connector fitting for aspiration and a second connector fitting for gas injection, with the second connector used after the first connector is no longer in use.

[0077] According to another aspect, there is a need for a suitable device for integrity testing, capable of testing connections adjacent to attachment components having one or more gas-permeable ends. To this end, a device is provided for detecting detectable gases in a test chamber of a hermetically sealed environment, the device comprising a sealing arrangement according to the invention for positioning within the test chamber.

[0078] This device typically includes:

[0079] - A sterile container for positioning within a detection chamber, the container having a flexible body that at least partially defines an internal chamber for receiving and containing a detectable gas without leakage;

[0080] - A sealing arrangement, which is arranged such that the fluid passage of the connecting device is selectively in communication with the internal volume of the housing unit and with the internal chamber;

[0081] - A hose, comprising a flexible hose end connected to a first annular portion of a connecting device, and allowing fluid communication between the at least one gas-permeable end and the internal chamber; and

[0082] - A sensor device associated with a detection chamber and capable of sensing detectable gas outside the inner chamber in the detection space of the detection chamber due to leakage.

[0083] The housing unit and sealing structure hermetically separate the internal volume from the detection space, wherein the attachment member having at least one gas-permeable end is received within the internal volume.

[0084] With this arrangement, the device is suitable for tightly separating the internal chamber, which serves as the tracer gas accumulation chamber, from the detection space.

[0085] The device may also include a pumping assembly for generating a pressure differential between an internal chamber (a detectable gas accumulation chamber) and a detection chamber.

[0086] In some embodiments, the device further includes a detectable gas source and a valve associated with the detectable gas source. A connection device and a flexible hose end are joined at a coupling area to form a fluid transfer assembly. The internal chamber is configured to: when the valve is open, fill the internal chamber with the detectable gas through an injection line communicating with a fluid passage via the internal chamber.

[0087] Optionally, a clamping collar is provided around the connection area, the collar being configured to permanently deformably press against the overlapping portion between the flexible hose end and the handle of the first annular portion with barbs. The handle may typically extend between the shoulder or adjacent portion (included in the connection device) and the barbs of the first annular portion.

[0088] Furthermore, embodiments of the present invention provide a method for monitoring leakage of a fluid transfer assembly for fluid communication between two fluid receiving portions using a sealing arrangement according to the present invention, the fluid transfer assembly being particularly suitable for use in biopharmaceutical assemblies, the method comprising:

[0089] During the preparation stage:

[0090] - Connect the connecting device to the hose to obtain a connected state of the fluid transfer assembly, the connecting device forming a first fluid receiving portion of the two fluid receiving portions, the connection including inserting a first annular portion, which is a male portion, into the hose at the end of the flexible hose formed as a female portion, the hose forming all or part of the second fluid receiving portion of the two fluid receiving portions;

[0091] -A ring-shaped contact area is defined at the connection area where the end of the flexible hose overlaps the first annular portion;

[0092] - Assemble the sealing arrangement such that the fluid passage selectively communicates with the internal volume of the housing unit; and

[0093] Then, during the testing phase:

[0094] - The tracer gas is injected into an accumulation space separated from the detection space by an annular contact area, so as to accumulate the tracer gas in the fluid passage, wherein the detection space is located in an airtight detection chamber;

[0095] Therefore, any escape of tracer gas through possible defects in the annular contact area can be detected in the detection space by a tracer gas sensor device that is in fluid communication with the detection space.

[0096] Typically, the testing phase is suitable for determining whether the annular contact area hermetically separates the detection space from the accumulation space.

[0097] In some embodiments, the tracer gas is fed via an injection line connected to a flexible bag or pouch. In a variant, one housing portion includes a connector for a hermetically sealed connection to the tracer gas injection line.

[0098] Vacuum suction can be performed inside at least one of the two fluid receiving sections, preferably in both fluid receiving sections, and the channel is used for vacuum pumping a certain amount of air present in the connecting device.

[0099] Optionally, the detection steps performed by the sensor device associated with the detection space may include measuring information representing the partial pressure of a tracer gas (e.g., helium) in the detection space. A mass spectrometer associated with a vacuum pump can be used for such vacuum pumping. If the presence of the tracer gas is not detected, or if the partial pressure of the tracer gas is not considered to reflect a leak, an annular contact forms a sealed contact area that has passed a test, which can be a 2 μm test or any similar test for detecting any defects (e.g., with the ability to detect defect sizes smaller than 10 μm).

[0100] Then, in subsequent steps, the method may include comparing test results obtained using a sensor device, representing a decrease in the partial pressure of the tracer gas in the detection space, with at least one reference result to determine whether the connection of the fluid transfer assembly is considered to have passed test / integrity verification. This step can be automated to improve testing speed.

[0101] Flexible plastic bags can form part of, or be construed as, a bag arrangement including flexible tubing, each bag being suitable for receiving biopharmaceutical products. This test is performed prior to any filling step involving the filling of such biopharmaceutical products.

[0102] Using this method, sensitivity can be very good, and all steps in the testing phase can be performed in the same measurement cycle (e.g., without changing the suction performed by at least one vacuum pump).

[0103] In various embodiments, it is also possible to use one or more of the following features, either alone or in combination:

[0104] Using a feed line or similar injection line, the port of the flexible bag connects the flexible bag (connected to a hose) to a pressurization system that includes a gas tracer supply device (gas source).

[0105] - The pressure control device functions as a control unit to vent air from the internal volume and optionally from the bag (connected to the hose).

[0106] - The pressure control device is configured to perform the following steps in sequence: emptying the bag / injecting tracer gas into the connection device and housing unit, and into the accumulation space / measuring the leakage rate of the gas tracer or any suitable parameter indicating tracer gas leakage.

[0107] - Provide a valve arrangement including at least one valve disposed between a pressurized helium or similar tracer gas source and a supply line.

[0108] - The valve arrangement includes at least one valve disposed between the vacuum pump and the accumulation space.

[0109] In various embodiments, it is possible to use one or more of the following, alone or in combination:

[0110] - Each bag or at least one bag, including the components of the connecting device, has an outer cover / wall that defines a single internal space of the bag;

[0111] - The outer wall of the bag includes a port that is adapted to be closed or adapted to be fluid-tight and removably connected to the mass spectrometer, possibly via a tube connection;

[0112] - The bag is equipped with filling and / or discharge tubes located outside the outer sleeve / wall.

[0113] - The bag may include one or more connectors, filters, and sensors. Attached Figure Description

[0114] The figures in the accompanying drawings will now be briefly described.

[0115] Figure 1 This is a perspective view of a sealing arrangement according to one embodiment, in a configuration where no hoses are yet connected.

[0116] Figure 2A This is a view of a biopharmaceutical assembly with several flexible tubing, one of which can be formed into a catheter or tubing for connection. Figure 1 The connecting device shown has a hook-shaped nozzle.

[0117] Figure 2B This is a detail of a longitudinal sectional view of the fluid transfer assembly obtained at the first annular portion of the connecting device, which belongs to... Figure 1 The sealed arrangement.

[0118] Figure 3 It is similar to Figure 1 The view is shown, but the housing portion of the housing unit has been removed, making the attachment parts of the connecting device visible.

[0119] Figure 4 It is used for Figure 1 and Figure 3 A perspective view of an exemplary sealing structure in an embodiment.

[0120] Figure 5 This is a schematic cross-sectional view of the interior of the housing unit, showing the sealing structure sandwiched between the housing parts.

[0121] Figure 6 This schematically illustrates the use of a flexible container / bag and one or more associated connections (including...) for testing flexible containers / bags. Figure 1 An example of a testing system for the integrity of a sealed connection device and a hose connected to a flexible container / bag.

[0122] Figure 7 A connection device is shown that can be supported by a ring or any suitable annular component to ensure airtightness when in contact with the housing portion.

[0123] Figure 8 A pair of exemplary connection devices are shown that can cooperate to achieve a sterile connection of biopharmaceutical fluids, wherein the membrane is adapted to be removed after initial interlocking.

[0124] Figure 9 It is similar to Figure 3 The view shows that the housing portion has an outwardly extending connector fitting that allows for direct suction within the housing unit. Detailed Implementation

[0125] The following provides a detailed description of several embodiments of the present invention with reference to examples and accompanying drawings.

[0126] In all the figures, the same reference numerals are used to denote the same or similar elements. For better illustration, some dimensions or thicknesses may be exaggerated.

[0127] The described embodiments are illustrative and should not be construed as limiting the scope of the invention. Features from one embodiment or aspect can be combined with features from any other embodiment or aspect in any suitable combination. For example, any individual or collective feature of a method aspect or embodiment can be applied to an apparatus, product, or component aspect or embodiment, and vice versa.

[0128] Figure 1 and Figure 2B A connecting device 1 is shown, which has a barbed nozzle 1a or similar male portion suitable for assembling the hose end 11a of a flexible hose 11 (flexible tube, etc.). This insert end or male portion is configured to be inserted into the distal end 11 of the flexible hose, such that the hose 11 extends on one or more barbs B. Figure 2A As shown, this flexible tube 11 can be attached to a flexible container commonly referred to as a bag (e.g., a 3D bag 40 or a 2D bag 40'). The 2D bag 40' (e.g., Figure 6 As shown, the 3D bag 40 remains relatively flat in the filled state because its periphery is sealed to remain planar, while the 3D bag 40 has a parallelepiped volume when filled with fluid, and this bag 40 has gusseted plates.

[0129] refer to Figure 1 , Figure 3 and Figure 8 The connecting device 1 or 1' can be a single tubular member extending about the longitudinal axis X. Here, the connecting devices 1, 1' include a tubular portion extending from the first annular portion 101 to the second annular portion 102 or 102'. Such the second annular portion 102, 102' is intended for attachment to a complementary portion after the hose 11 has been tightly connected to the first annular portion 101. The gas-permeable end 1b of the connecting device 1 is included in the attachment member 15 or 15' of the connecting device 1, 1', which is disposed at the second annular portion 102, 102'.

[0130] To allow for integrity testing of the hose connection at the first annular portion 101, the second annular portion 102 can be accommodated within the internal volume V defined by the housing unit 2. (Reference) Figure 1 and Figure 5 The housing unit 2 can be an outer cover made of at least two housing parts 201, 202. The first housing part 201 and the second housing part 202 can be assembled by forming a peripheral seal at the joint between two complementary connecting edges 24, 25 of the respective housing parts 201 and 202.

[0131] The housing unit 2 may have two wall portions W1 and W2, which are the same wall, defining a channel 20 for the intermediate portion 1c of the connecting devices 1 and 1' to pass through the wall of the housing unit 2. Typically, the housing portions 201 and 202 may be hollow, thus forming two complementary shells. Walls with proximity to the channel 20 may be distributed within these two shells. In a non-limiting embodiment shown, this configuration with hollow housing portions 201 and 202 is suitable for enclosing attachment members 15 and 15' with outer diameters significantly larger than the intermediate portion 1c and the first annular portion 101. In some variations, only one of the housing portions 201 and 202 is hollow and defines an internal volume V.

[0132] refer to Figure 1 , Figure 5 and Figure 6 The connecting device 1 and the housing unit 2 cooperate, with only the first annular portion 101 available outside the housing unit 2, while the second annular portion 102 extends entirely within the internal volume V, beyond the access channel 20 or similar opening. Here, the connecting device 1 is fixed relative to the housing unit 2 due to the clamping action around the middle portion 1c extending through the access channel 20. Figure 1 As shown, an assembly structure is obtained, in which the housing unit 2 is in a closed state. There is no leakage path between the intermediate portion 1c and the walls (W1, W2) defining the access channel 20, because the intermediate portion 1c maintains an airtight connection with the sealing structure 4 (forming all or part of the peripheral seal) installed between the housing portions 201, 202.

[0133] like Figure 4 and Figure 5 As shown, the sealing structure 4 can have two separate segments JP1, JP2, forming an annular inner contact edge, thus providing a continuous annular ring R4 near the channel 20 in the assembly configuration. Here, the ring R4 extending around the central axis X' coaxial with the tubular portion of the connecting devices 1, 1' can be included in the sealing structure 4, thereby obtaining the following radial contact area near the channel 20 due to the sealing structure 4:

[0134] -The outer area of ​​the housing unit with a sealed structure (using the lower end face F1 of the first deformable member / component 4a and the upper end face F2 of the second deformable member / component 4b); and

[0135] -Features a sealed structure-intermediate part contacting the internal area (using the internal end faces f1, f2 of two separate segments JP1, JP2).

[0136] The internal end faces f1 and f2 are typically included in the bridging portions that form segments JP1 and JP2. Alternatively, they are formed as symmetrical bridging portions (in a mirror-inverted arrangement). Of course, the geometry (size, shape) of the sealing structure 4 can vary depending on the specific geometry (size, shape) of the intermediate portion 1c of the fluid passage 8 surrounding the connecting devices 1 and 1' and the housing unit 2.

[0137] Using this sealing arrangement 100, testing is permitted in the detection chamber CH. Figure 2B and Figure 6 During the integrity test of the hose connection shown, the gas circulating in the connection device 1 through the opening O and escaping from the fluid passage 8 through the gas-permeable end 1b is hermetically contained in the internal volume V of the housing unit 2 (without escaping into the detection space toward the detection chamber CH).

[0138] The channel 20, defined by the housing unit 2, for fastening the connecting devices 1 and 1', is sized and shaped to fasten the devices 1 and 1' at the intermediate portion 1c by opposing compressive forces. Due to the sealing structure inserted between the intermediate portion 1c and the walls W1 and W2 of the housing unit, this opposing compressive force is converted into radial compression, and the intermediate portion 1c and the walls W1 and W2 of the housing unit accordingly push the sealing structure 4 in opposite directions (perpendicular to the mating plane P, which will be described in further detail below).

[0139] Exemplary embodiments of the connection device

[0140] The illustrated connecting device 1 extends linearly and has a connector / barbed nozzle forming a first annular portion 101 for the hose 11 and an attachment member 15 for aseptic connection with a corresponding attachment member 15' disposed in the complementary connecting device 1'. Here, the housing unit 2 is adapted to... Figure 8 Any of the connecting devices 1 and 1' shown cooperate because they have the same or similar intermediate portion 1c, which is adapted to form a sealing structure-intermediate portion contact against the inner end faces f1 and f2.

[0141] The opposite end annular portions 101, 102 are aligned here, but this disclosure is not limited to use with straight / linear fittings or connecting devices, but can also be applied to other assembly components. For example, bend fittings or fittings that divert or merge fluid flows through them can be provided. The cavity or fluid passage 8 can extend from the first opening O included in the first annular portion 101 to the second opening O' included in the second annular portion 102. More generally, it should be understood that the connecting devices 1, 1' can be provided with two opposite openings O, O', and the second opening O' may be covered when extending within the internal volume V of the housing unit 2.

[0142] To protect the second opening O', a cap 130 or a similar rigid or relatively rigid plugging element can be provided. (Reference) Figure 3 The cap 130 may include a bottom and a ring-shaped skirt to cover all or part of the attachment parts 15, 15' laterally. (See reference) Figure 8 The cap 130 may directly cover the attachment member 15, or it may cover a movable collar C that is displaceable relative to the attachment member 15'. Here, such collar C may be a locking device for the connection between the members 15, 15', which surrounds at least one of the members 15, 15' in a sterile connected state.

[0143] The tubular portion defining the fluid passage 8 can be a single piece made of molded plastic material. This material is incompressible in the intermediate portion 1c. Compared to the cross-section at the free end defining the opening O, a portion of the intermediate portion 1c has an enlarged cross-section. Here, the gripping area of ​​the connecting devices 1, 1' is obtained in this enlarged cross-sectional portion.

[0144] Typically, attachment members 15, 15' located at the second annular portion 102 are radially fastened to the central tube segment of the second annular portion 102 in a fixed manner. The free end of the central tube segment defines a second opening O'. An end flange or annular edge is provided around the opening O to form a receiving surface, and a film 36 covering the opening O' is detachably adhered to the receiving surface.

[0145] Since membrane 36 has no barrier effect against gases, particularly helium or similar tracer / detectable gases used in integrity testing, the corresponding ends of connecting devices 1, 1' at the second tubular portion 102 are gas-permeable ends 1b. Each membrane 36 can be folded so that it can be unfolded when the two connecting devices 1 and 1' are attached via attachment parts 15, 15'. Connecting devices 1, 1' can be male-type components (e.g., Figure 8The type of attachment 15 shown, the male part uses a locking slider and clip or similar locking member to the female part ( Figure 8 The attached component 15' shown cooperates with each other.

[0146] The connecting devices 1 and 1' shown in the diagram are from the applicant. SFT Aseptic Connector Series. In biopharmaceutical manufacturing operations, connectors 1, 1' allow for rapid and reliable aseptic connection and aseptic fluid transfer between two separate, pre-sterilized process components. Each membrane 36 may be a sterile-grade polyethersulfone (PES) membrane. The connectors or attachments 15, 15' involved in locking the connection are equipped with error-proofing mechanisms, such as sliding or similar guidance in the connection area along a direction perpendicular to the longitudinal direction of connectors 1, 1', or rotation along the longitudinal axis X.

[0147] Membrane 36 can be configured, for example, to be coupled at the traction end, thereby allowing both membranes to be removed simultaneously before locking the connection between components 15, 15'.

[0148] exist Figure 1 or Figure 7 In the example shown, the barb B is disposed near the opening O at the end of the fluid passage 8, which is in the peripheral region adjacent to or defining the opening O of the connecting device 1. In some embodiments, more than one barb B may be formed adjacent to the opening O. The barb B may extend circumferentially around the fluid passage 8.

[0149] refer to Figure 2B The barb B can provide a tapered surface 44 from the largest diameter portion of the barb toward the insertion end. The insertion end corresponds to the opening O. Optionally, the connecting devices 1, 1' may include a shoulder, collar, or similar adjacent portion BP to limit the insertion range of the insertion end into the corresponding conduit defined by the hose 11. Optionally, a substantially cylindrical shank 46 may be defined as the portion of the connecting device 1 located between the barb B and the shoulder formed by the adjacent portion BP. The barb-type nozzle 1a here is composed of the shank 46 and a connector end portion provided with said one or more barbs B.

[0150] The adjacent portion BP may be a transition between the handle portion 46 and the grip portion 105, and optionally, it is provided with ribs, here longitudinal ribs.

[0151] Once the other annular portion 102 has been securely fastened to the housing unit 2, Figure 2B The connection shown (the fluid connection between the annular portion 101 and the associated hose 11) can be a connection under test. Thus, the fluid transfer assembly 200 (see also...) is obtained. Figure 8This is suitable for fluid to flow out of or into the internal volume of hose 11 through fluid passage 8. When hose 11 is already connected to bag 40 or 40', for example with... Figure 2A The bag shown is 40 or Figure 6 When the internal volume V40 of the bag-shaped object 40' shown is in fluid communication, the tightness of this fluid connection can be controlled.

[0152] Exemplary structure of bag component

[0153] Figure 2A Component 7 illustrates that hose 11 can be adapted for transferring fluid within a fluid transfer loop (when coupled to connection devices 1, 1') and / or adapted for forming a connection at at least one supply or transfer port 22 of a container (such as flexible bag 40). Flexible bag 40, which may contain a large biopharmaceutical fluid capacity, can form a receiving volume for biopharmaceutical fluid transferred via the connection. Fluid connection device 10 can be included in container 40 and can be provided in manufacturing steps of the biopharmaceutical industry, in one or more stages of research and development, for any suitable fluid transfer application with quality control, for delivering fluid to a filtration stage, and these examples are not limiting. The same applies to hose 11 connected to the barbed nozzle 1a of fluid connection devices 1, 1'.

[0154] Bag 40 here is in the form of a flexible bag that can initially be folded flat. Bag 40 is typically defined as a flexible shell essentially defined by a set of walls. One of the container walls (receiving wall) may integrate at least one port connector assembly. This also applies to Figure 6 The bag-like structure 40' is shown. More generally, this set of walls or "receiving walls" forming the containers 40, 40' defines a fluid space V40 that is in communication with the circulation volume of the hoses and connecting devices 1, 1', and thus with the fluid passage 8.

[0155] refer to Figure 2B It can be understood that a connection area corresponding to the portion where the flexible hose end 11a overlaps the barbed nozzle 1a or similar annular portion 101 is obtained. Therefore, the corresponding open end 11o of the hose 11 ( Figure 6 It can extend beyond the radially deformable area of ​​the flexible hose end 11a, where one or more annular sealing contact areas SC are provided between the tubular outer surface of the annular portion 101 (defined here by the barb B) and the inner end face of the flexible hose end 11a.

[0156] The barbed nozzle 1a is suitable for connecting the connecting devices 1, 1' and the containers or bags 40, 40' of the biopharmaceutical product via a flexible hose end 11a. A fluid connection device 10 is provided for assembling this flexible hose 11 to a connector disposed in a transfer port 22 in the container or bag 40, 40'. Here, the transfer port 22 can be connected to the end of the flexible hose 11 opposite to the flexible hose end 11a, which overlaps with the barbed nozzle 1a. Because the flexible hose end 11a surrounds the barbed portion forming the nozzle 1a, a tight connection is generally obtained, except in the case of defects. Tracer gas testing is advantageous in preventing the use of insufficiently tight connections, i.e., connections where defects of approximately 2 μm or larger can be detected.

[0157] Given Figure 2A Component 7, as understood, allows for the creation of one or more connecting devices 1, 1' to establish a fluid transfer loop, for example, by connecting to a bag / container arrangement. A container arrangement comprising one or more flexible disposable bags 40, 40' can be assembled and then subjected to an integrity test. Each flexible disposable bag 40, 40' has an inlet element or port to which a flexible connecting tube / hose is attached (using a sterile connection). A sterile connector can be provided at the inlet end. Reference Figure 6 The container arrangement / assembly 18 may be provided with one or more clamps or clamping mechanisms for holding the hose. Clamps made of a material harder than the material of other parts of assembly 18 may be provided to selectively isolate the respective bags 40 or 40'.

[0158] More generally, the connecting devices 1 and 1' can be used in any kind of container arrangement 18, which includes one or more bags 40, 40' or an arrangement with two complementary devices connected by a coupling between the connecting devices 1 and 1'.

[0159] Typically, such as Figure 1 and Figure 8 The connecting devices 1, 1' shown are separate from the containers 40, 40'. The connecting devices 1, 1' preferably belong to a fluid transfer assembly 200 separate from any wall of the container / bag 40 or pouch 40'. When preparing for integrity testing, the connecting devices 1, 1' are assembled in the sealing arrangement 100 such that the permeable end 1b is sealed within the internal volume V of the housing unit 2. The hose 11 is also connected to the first annular portion 101 and allows communication with the tracer gas by connecting to the pouch / bag 40, 40' that receives the gas (injected via a suitable injection line L) or possibly by direct connection to the tracer gas supply section.

[0160] refer to Figure 6 In the preparation stage prior to the integrity test, a bag assembly 18 is prepared by connecting the flexible hose end 11a to form a fluid transfer assembly 200. This bag assembly 18 is placed inside the test equipment, within the test chamber CH. An injection line L is fully connected to the bag 40', allowing the injection line to selectively supply a tracer gas (e.g., helium or argon) within the internal space defined by the bag assembly 18 (including the fluid passage 8). This establishes a pressure differential between the internal space and the test chamber (hereinafter referred to as the test chamber CH). The housing unit 2 forms an airtight barrier between the internal space and the test space of the test chamber CH. The annular contact area SC at the connection region where the flexible hose end 11a overlaps with the handle 46 (see...) Figure 2B Therefore, it was also tested because any leak at that location would cause the tracer gas in passage 8 to escape into the detection chamber CH.

[0161] Based on the dimensions of the inner cavity or fluid passage 8 and the wall thickness of the first annular portion 101, the hose 11 may have an inner diameter selected for suitability for use with a barbed nozzle. Depending on the application of the hose 11, the inner surface and wall thickness of the hose 11 may be selected to ensure suitability for withstanding internal fluid pressure. The hose 11 may be a single-walled conduit. More generally, the use of a single-walled conduit may be preferred to minimize any voids that may occur between the walls of a multi-walled conduit, which could create opportunities for leakage or bacterial growth.

[0162] According to some embodiments, the surface contact between the barb B and the hose 11 is considered sufficient to secure the hose 11 to the annular portion 101 of the connecting devices 1, 1'. In other embodiments, fasteners (e.g., cable ties, ear clips, or similar clamping collars 48) are secured around the hose 11 along a region of the handle 46, preferably selectively around the handle region.

[0163] The annular end edge of the distal portion of hose 11 is not surrounded by this clamping collar. Because this annular end edge has been temporarily deformed and widened, it cannot typically ensure a tight contact around the handle 46. (Reference) Figure 2B Due to the clamping collar 48 (or other relatively rigid element, or resilient sleeve or similar sleeve), the hose 11 can be secured to the barb B by forming a seal between the barb B and the inner surface to minimize or suppress gas leakage between the two. In the connection area, the flexible hose end 11 has a distal portion surrounding the handle 46 that deforms less (in the connected state) than the proximal portion surrounding the barb B to create this seal.

[0164] In the option of adding a crimping collar 48 around the end portion of the hose, after obtaining the annular contact area SC, the crimping of the collar 48 can be performed in the shank region so that the inner diameter of the collar is reduced to below the maximum outer diameter of the hose end (at the barb B). The additional contact area ZC between the crimping collar 48 or similar clamping rings is longitudinally located between the adjacent portion BP and the barb B, extending longitudinally between the adjacent portion BP and the barb B, here around the cylindrical shank 46.

[0165] Although the accompanying drawings show an embodiment with a single clamping collar 48, any suitable binding element (possibly a pair of binding elements) can be used to provide a clamping effect and ensure that the hose 11 is not accidentally removed in order to perform the reinforcement steps. In some variations, the collar 48 may be replaced by a single-layer sleeve, a multi-layer sleeve, or a combination of a sleeve or liner and a more rigid collar (e.g., a resilient sleeve or liner and a metal sleeve / collar).

[0166] The fluid transfer assembly 200 can be obtained in various ways. Here, such a fluid transfer assembly is obtained once the insertion end 11a of the hose 11 overlaps with the barbed nozzle 1a. The hose 11 can be inserted until all or part of the flexible hose end 11 abuts the adjacent portion BP. Additionally or alternatively, the barbed nozzle can be inserted until the flexible hose end 11a reaches the channel 20 or extends partially within the internal volume V.

[0167] refer to Figure 2B The fluid passage 8 may have a longitudinal axis A, which is the central axis of the second annular portion 102. In the closed state, axis A corresponds to the central axis of channel 20. This axis may also correspond to the longitudinal axis X of the connecting devices 1 and 1'.

[0168] Installation of sealing structure on housing unit

[0169] The housing portions 201 and 202 are typically incompressible, allowing housing unit 2 to compress sealing structure 4. In the first embodiment, as... Figure 1 and Figures 3-5 As shown, the joint between housing portions 201, 202 extends primarily in a planar manner. In this embodiment, the first housing portion 201 and the second housing portion are identical. The channel 20 defined by housing portions 201, 202 (here between the two walls W1, W2) has an extension length corresponding to the thickness e of the front wall of the housing unit including said two walls W1, W2. One or both slots in housing portions 201, 202 may form the channel 20. Two semi-circular slots may be preferred to facilitate surrounding the intermediate portion 1c without confusion during assembly operations.

[0170] like Figure 5As shown, the compressible sealing structure 4 can extend in an interface groove G obtained by recessed segments in the thickness of the housing unit sidewall. Here, this interface groove is an internal groove, so that the sealing structure is generally not visible from the outside when the housing unit 2 is closed. In a variant, the sealing structure 4 extends at the joint between housing portions 201, 202, and extends beyond the external end face and / or beyond the internal end face of the housing unit 2.

[0171] The sealing structure 4 may include or comprise two sealing members 4a and 4b, which are preferably two separate pieces. More generally, the sealing structure 4 includes at least one piece sandwiched between the following components:

[0172] -A first rigid member forming all or part of the first housing portion 201, and

[0173] - A second rigid member that forms all or part of the second housing portion 202.

[0174] In the first embodiment, the two deformable sealing members 4a and 4b, both made of elastic plastic material, include:

[0175] - Two basic planar parts J1 and J2, which are parallel to each other and connected to each other in the closed state (having an interface contact part C4, which is the direct contact part between these planar parts), and

[0176] - Ring R4, which is complementary to the two planar portions J1 and J2.

[0177] Ring R4 typically surrounds and encloses the middle portion 1c.

[0178] Before closing the housing unit 2, the first sealing member 4a can be installed in the lower recessed portion belonging to the first housing part 201. (See reference) Figures 3-5 The first sealing member 4a has a semi-circular portion or a similar curved portion, forming the first segment of two separate segments JP1, JP2. Then, the connecting device 1 (or device 1') is fastened to the first housing portion 201, with a portion of the intermediate portion 1c resting on the inner end face f1. The intermediate portion 1c extends (temporarily) through a corresponding slot in the first housing portion 201.

[0179] Alternatively, this internal end face f1 may extend below (in this case, completely below) the mating plane P of the joint between the sealing members 4a and 4b. This end face f1 is typically semi-circular and / or fully matches the shape and size of the contact area in the intermediate portion 1c. The internal end face f1 is included in a first segment JP1 belonging to the first sealing member 4a. Due to the slot in the first housing portion 201, this first segment JP1 can be received in a recessed portion offset downwards compared to the rest of the interface recess G. Similarly, due to the slot in the second housing portion 202, another recessed portion can be offset upwards compared to the rest of the interface recess G.

[0180] Once the intermediate portion 1c has been positioned to contact the first sealing member 4a and extend through the slot between the walls of the first housing portion 201 for positioning the attachment member, the housing unit 2 can be closed by applying the second sealing member 4b around the intermediate portion 1c to complete the first sealing member 4a, thereby forming a ring R4 at the intermediate portion 1c around the corresponding segment of the connecting device 1.

[0181] To form this sealing ring R4 without requiring precise manipulation of the sealing components by the operator, each of the sealing components 4a and 4b can be pre-fastened to the corresponding housing portion 201 or 202. Interlocking protrusions and / or guides can be provided at the connecting edges 24 and 25 of the housing portions 201 and 202.

[0182] In the closed state, ring R4 can extend perpendicularly to the mating plane P where its planar portions J1 and J2 contact each other; as Figures 4-5 As shown.

[0183] The connecting edges 24 and 25 allow for compression of the sealing structure 4, and the sealing members 4a and 4b may deform radially (parallel to the thickness direction of the housing unit sidewalls). In practice, the housing portions 201 and 201 are rigid, and in the closed state, the height of the gap between the connecting edges 24 and 25 may be less than the nominal size / section height of the sealing structure. In the first embodiment, this gap is obtained at the interface recess G, and the gap height is measured perpendicular to the longitudinal axis X of the connecting device 1 and generally perpendicular to the mating plane P.

[0184] The sealing structure 4 typically surrounds the intermediate portion 1c extending through the front wall in the intermediate region between the bottom and top walls of the housing unit 2. In the closed state, the front wall (comprising two walls W1, W2) extends from the bottom wall to the top wall, for example, perpendicular to both the bottom and top walls. In a variant, the housing unit 2 has a circular geometry and / or includes a top wall that is not parallel to the bottom wall.

[0185] Clamping can be performed to lock the housing unit 2 in a closed state, wherein the sealing structure 4 elastically deforms at the peripheral seal. For example, the sealing arrangement 100 is provided with a clamping member 23 arranged around the periphery of the housing unit 2 around the internal volume V to maintain the sealing structure 4 in a compressed state. The two rigid members forming the housing portions 201, 201 can be clamped together to compress the sealing structure 4 (clamping with a constraint effect to deform the cross-section of the sealing members 4a, 4b). The clamping member 23 may be provided with screws and / or bolts, pull rods, clamping rods, or one or more of any suitable clamping assemblies. These members allow for removable connections. In fact, after the integrity test, the housing unit is disassembled without any risk of altering the tested connections (simply removing the two housings with the associated sealing members 4a, 4b).

[0186] In the first embodiment, rings R4 are distributed in members 4a and 4b, and are thus formed after the second annular portion 102 is received in the housing portion of housing unit 2. In the second embodiment and some variations, such as Figure 7 As shown, ring R4' can be a single piece and / or attached around the intermediate portion 1c prior to assembling housing unit 2 to obtain sealing arrangement 100. In some alternatives, this ring R4' can be shrinkable (as shrink packaging material) to form a shrink seal. Possibly, the sealing structure has a flat portion different from ring R4' and provided with a contact end, which is also compressed to form an airtight contact against ring R4'. This flat portion may have been fastened to at least one of housing portions 201, 202, thereby forming a peripheral seal defining the portion or the entire circumference.

[0187] More generally, it can be understood that one or more portions (possibly two planar portions J1, J2) involved in the interface between the rings R4, R4' or similar annular layers of deformable material surrounding the intermediate portion 1c and the sealing connection edges 24, 25 are complementary.

[0188] Furthermore, the cross-section of each sealing member 4a, 4b (which may be identical) can vary. This cross-section can vary, for example, being flat or planar at least in individual portions J1, J2 that do not contact the intermediate portion 1c. Additionally, the sealing structure 4 can have a circular, elliptical, or H-shaped cross-section (in the latter option, the sealing structure 4 can clamp the corresponding wall edges of the housing portions 201, 202).

[0189] Materials used in sealing arrangements

[0190] The connecting device 1 can be an assembly formed by molding, casting, additive manufacturing, or other known processes. The connecting device 1 can be made of thermoplastics, such as polyolefins, polypropylene, polyethylene, polyoxymethylene (POM), polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), polyamides, polysulfones, polyesters, polycarbonates, and glass-filled thermoplastics. The connecting device 1 can also be made of thermosetting materials (e.g., epoxy resins, phenolic resins, silicone resins, and copolymers of silicone and phenolic resins). Other suitable materials may include cyanate esters, polyurethanes, and polyurethane methacrylates.

[0191] The housing unit 2 can be made of any suitable rigid material (typically a metal). The internal volume V can be defined by an internal end face made of stainless steel. The housing unit 2 can be hinged, for example, to guide movement of the housing portion 202, which acts as a cover, relative to the complementary housing portion 201.

[0192] The sealing structure 4 is made of a flexible material (such as silicone or TPE). This flexible material is not porous (and is generally not hollow) and is suitable for providing a gas barrier effect. This sealing material can be compressed, allowing the thickness of the sealing structure to be elastically reduced, thus the sealing structure 4 is compressible, preferably with a thickness reduction of at least 10%.

[0193] The flexible tubing 11 is preferably a flexible catheter suitable for medical or pharmaceutical environments. The flexible tubing 11 can be made of thermosetting or thermoplastic polymers. If thermosetting materials are used, silicone, polyurethane, fluorinated elastomers, or perfluoropolyethers are preferred construction materials for the catheter. If thermoplastic plastics are used, Pipes, block copolymers of styrene-ethylene-butene-styrene, PureWeld, PVC, polyolefins, or polyethylene are preferred construction materials. In some alternatives, a flexible hose 11 made of ethylene-vinyl acetate (EVA) may be preferred because it allows components made of EVA to be welded together.

[0194] The flexible hose 11 here has a circular cross-section and a characteristic outer diameter and a nominal inner diameter. This diameter is a constant dimension, so the thickness of the hose can generally be constant. A hose with a thickness less than or equal to 5 mm is likely preferred, and this thickness is generally not less than 0.5 mm (to provide sufficient mechanical strength). The thickness can range from 1.5 to 3.2 mm. In some alternatives, the hose material can be translucent or transparent. The connecting devices 1 and 1' can be made of opaque material.

[0195] Exemplary use of sealing arrangement in integrity testing

[0196] refer to Figure 6The method of performing tests on the connection of the fluid transfer assembly 200 can be seen. After the preparation phase, the fluid transfer assembly 200 can be tested individually or together with the bag assembly 18. When the bags or pouches 40, 40' are connected to the connecting devices 1, 1' via the hose 11, a reinforcement step can optionally be performed during the preparation phase, such as using a clamping collar (possibly a crimping collar 48). The connection can be made with or without the clamping collar 48. Clamping the portion of the flexible hose end 11 around the handle 46 using the collar 48 helps prevent any accidental removal of the flexible hose end 11a (due to fluid pressure). Figure 2B As shown, the clamping collar 48 can also help limit leakage points at the rear of the barb due to air gap 66. However, this effect may depend on how the collar is installed / clamped / crimped.

[0197] The device used for integrity testing is a device equipped with a hermetically sealed test chamber CH. The device may have a fixed body or base with a sealed enclosure. A sealing member (not shown) is provided for removably receiving a cover member, which may be a hollow cover member or a plate member. In the assembled state using the sealing member, the cover member and the body form the test chamber CH.

[0198] This device is suitable for use in the following applications:

[0199] - Inject a detectable gas (tracer gas, such as helium or argon) into the detection chamber CH, more particularly into the bag assembly or similar system being tested; and

[0200] - In the event of a leak, detect this gas in the detection chamber CH.

[0201] Here, the system under test is a sterile container 40, 40' located in the detection chamber CH. This container has a flexible body that at least partially defines an internal chamber 42 for receiving and retaining the detectable gas without leakage. Of course, the part under test can be any of a large number of different devices, with at least one sealing arrangement 100 provided. (Reference) Figure 6 The device includes a sealed arrangement 100 for positioning in the detection chamber CH, and a hose 11 includes a flexible hose end 11o connected to a first annular portion 101, allowing fluid communication between a gas-permeable end 1b and an internal chamber 42.

[0202] The device has a pressurized tracer gas unit 14 or a similar gas source, which is provided with an injection channel 5. A valve V5 located outside the detection chamber can be provided to control the feeding of helium or a similar tracer gas through the injection channel 5. Optionally, the channel 5 communicates with a hose serving as a supply line L and is connected to a container forming the internal chamber 42. More generally, the tracer gas is supplied to the internal space of the system under test and flows through the fluid transfer assembly 200 to a gas-permeable end 1b, which is arranged inside the housing unit 2 of the sealing arrangement 100. The tracer gas cannot escape through the housing unit 2, thereby allowing testing of the connection with the hose end 11a. In effect, the housing unit 2 and the sealing structure 4 hermetically separate the internal volume V from the detection space within the detection chamber CH.

[0203] In some variations, housing unit 2 may be provided with a connector suitable for connection to a tracer gas injection line. A specific connector for the housing unit may be included in one of the housing portions 201, 202. In this variation, the tracer gas circulates in the internal volume V before reaching the fluid passage 8. This option is less preferred when bags or pouches 40, 40' are also tested, as the tracer gas filling time may be increased.

[0204] By Figure 9 The communication channel 50 formed by the connector fitting 51 shown in the alternative embodiment can be used for this connection with the tracer gas injection line and / or to allow suction relative to the outside of the membrane 36. This suction, performed directly within the internal volume V of the housing unit 2, can be a second suction combined with a first suction performed from the inside of the membrane 36. This first suction can use a line associated with the vacuum pump 16', which may include a portion of the supply line L for injecting the tracer gas.

[0205] When suction is also performed directly within housing unit 2, a faster vacuum can be established. More generally, access to the internal volume V (input and / or output pathways) can be provided at housing unit 2. When combined suction is established, gas diffusion through membrane 36 (which may depend on the type of membrane) is not a limiting factor in achieving a high vacuum at the end of suction. It should be understood that if additional input / output pathways are provided at housing unit 2, the evacuation of the internal volume V can be accomplished independently through this connection.

[0206] Still referencing Figure 6The device may include a pumping assembly for creating a pressure differential between the internal chamber 42 and the detection chamber CH. For example, a vacuum pump 16' may be present before the tracer gas injection to allow vacuum pumping. A vacuum is then obtained in the detection chamber CH. Two vacuum pumps may be present to evacuate each of the internal chamber 42 and the detection space (around the system under test), respectively. Evacuation must be performed to reduce the pressure in chamber CH.

[0207] In an alternative configuration where housing unit 2 has at least one connector fitting, a vacuum pump associated with connector fitting 51 can also perform suction to reduce the pressure in the internal volume V. Optionally, this pump is a vacuum pump independent of another vacuum pump 16'. In some configurations, this suction via communication channel 50 is performed by a suction line connected to an already available vacuum source, for example, using a branch line connected to the same vacuum pump 16'.

[0208] Alternatively, channel 5 can be used to vent the internal chamber 42 and obtain a vacuum or low-pressure state inside the system under test. Figure 6 An alternative arrangement for connecting this vacuum pump 16' to the same channel 5 is schematically shown. During the preparation phase prior to sensing the tracer gas, the vacuum pump 16' is selectively activated, while the tracer gas unit 14 is in an OFF or similar inactive state.

[0209] With the bag port and supply line / channel 5 connected, only after the hook-shaped nozzle 1a has been inserted into the flexible hose end 11a, thus obtaining, for example... Figure 2B Following at least one annular contact area SC (annular contact for sealing connection) shown, valve V5 can be actuated to selectively feed tracer gas into internal chamber 42. This annular contact is typically a sealing contact between the tapered surface 44 and the inner end face of the flexible hose end 11a.

[0210] The device also includes a sensor device 9 associated with the detection chamber CH and capable of sensing detectable gas outside the inner chamber 42 in the detection space of the detection chamber CH due to a leak in the system under test. A port 30 or tube separate from channel 5 is provided for connecting the sensor device 9 to the chamber CH. At least one valve may be used to control the suction associated with the port 30 communicating with the sensor device 9. For example, the valve may allow selection between a vacuum pump other than vacuum pump 16' and the tracer gas sensor device 9. In the test apparatus, the one or more valves may be solenoid valves.

[0211] The sensor device 9 may be in the form of a mass spectrometer or a similar detection device that is sensitive to the tracer gas in order to detect any leakage of the tracer gas. Here, the pressure around the system under test in the detection chamber CH may be low (higher vacuum, because no gas is injected). Therefore, the inner chamber 42 is a higher pressure chamber, while the detection space around the system under test (here, the bag assembly 18) is a lower pressure chamber.

[0212] Due to the full actuation of valve 5, at the beginning of the test phase, tracer gas is introduced into the higher pressure chamber, and a connection is established between the detection space (lower pressure chamber) and the sensor device 9.

[0213] The monitoring phase (testing phase) of the measurement cycle can be performed using the analysis module of a suitable control unit 13 after the aspiration step and tracer gas injection. At the beginning of the measurement cycle, the test equipment can be similar to a known system, as a low-pressure threshold needs to be reached after a waiting period. The pressure drop can then be analyzed to draw conclusions about the integrity of the system under test.

[0214] Any suitable analysis module 19 can be configured to set the appropriate partial pressure of the tracer gas (which represents leakage). In some alternatives, such an analysis module can be associated with or included in the tracer gas sensor device 9, and can:

[0215] - Using information representing the helium partial pressure, which is detected over a time period including the period following the injection step, typically when the aspiration mode is activated; and

[0216] - Compare the test results with at least one reference result to determine whether the connection is considered to have passed integrity verification.

[0217] In some alternatives, if helium (or other tracer gas) rapidly leaks from the accumulation space (here, internal chamber 42) into the detection space of the detection chamber CH (where the helium partial pressure is measured (and possibly displayed on a screen)), the distribution of the helium partial pressure will represent a rapid increase in the partial pressure. Analysis module 19 is therefore suited to confirm that the detected helium originates from internal chamber 42. If only the fluid transfer system 200 is tested, this means that a hole or defect exists at the connection area of ​​the fluid transfer assembly 200 under test, which cannot be considered leak-proof.

[0218] Conclusions regarding integrity depend on early detection of the tracer gas after the pressure drop. More generally, it should be understood that measuring / detecting any tracer gas partial pressure increase or similar suitable tracer gas parameters in the detection space is necessary to infer whether the connection has passed the tracer gas integrity test.

[0219] The control unit 13 can be adapted to coordinate the steps during the measurement cycle. This test can be effective for detecting very small defects. In some embodiments, a system that has successfully passed the test is considered to have no defects larger than a low size threshold (e.g., approximately 2 μm). Since this solution relates more specifically to the sealing arrangement 100, such a test apparatus will not be described in detail further.

[0220] Of course, the gas source connection step is typically performed after assembling the sealing arrangement 100 and after forming a connection around the first annular portion 101; this could be the barbed nozzle 1a. Therefore, before the assembly step involving the intermediate portion 1c, and before the connection step involving the connecting portion / barbed nozzle 1a, such as... Figure 6 The valve V5 shown, or any similar valve used for tracer gas injection, is normally kept closed. This valve is open during the injection step, which involves injecting tracer gas G into the internal chamber 42, prior to the analysis step performed by the analysis module 19 associated with the sensor device 9.

[0221] Each bag / pouch 40, 40' of component 18 can be tested using a vacuum chamber via fluid transfer component 200. The same vacuum chamber or different vacuum chambers can be used.

[0222] Of course, the evacuation step can typically be performed after clamping certain tubing / tubes, and the injection step can begin after evacuating the tested area / test space of the test chamber CH. The internal chamber 42 can be part of the internal volume of the entire arrangement / assembly 18 or circuit, and the clamp 3' (see...) Figure 2A It can be used to define an internal chamber that is small compared to the total fluid capacity of component 18.

[0223] Following testing, a disconnection step can be performed in which the supply line or channel 5 is disconnected from the biopharmaceutical disposable / sterile system equipped with hose 11, and the clamps (if present) are released. If the test is successful, the tested fluid transfer assembly 200 can be used in biopharmaceutical applications requiring a high level of integrity (e.g., compliance with 2μm testing).

[0224] The combination of continuous radial contact around the central portion 1c and compression in the radial direction is effective for forming a gas barrier.

[0225] While the detailed embodiments described above illustrate the use of a pressurized helium source 14 that typically contains helium (e.g., helium with a typical purity suitable for medical use), it is possible that different kinds of sources (possibly gas mixtures or helium with different purity levels) could be used to add the amount of helium injected around the flexible bag 2.

[0226] This test method is suitable for detecting leaks as small as micrometers, and even for large-capacity bags 40, 40' present in arrangement / component 18.

[0227] Therefore, by using housing unit 2 as a compact, built-in end complement to the internal chamber, a leak test kit for testing fluid fittings can be obtained without interfering with the connection being tested. Furthermore, when membranes are provided to cover the second opening O', they remain usable after removing housing unit 2.

[0228] Of course, the present invention is not limited to the above embodiments, which are provided merely as examples. The present invention covers various modifications, alternatives, and other variations that can be conceived by those skilled in the art within the scope of the present invention, and in particular covers any combination of the various operating modes described above that can be used alone or in combination.

[0229] For example, the middle part 1c is not necessarily like this. Figure 1 and Figure 8 The transition portion between the gripping portion 105 and the end members 15, 15' is shown. The gripping portion 105, or any other suitable portion, inserted between the attachment members 15, 15' and the barbed nozzle, can be received in the internal volume V, typically by extending beyond the annular contact area having flexible material compressed or squeezed by the housing unit 2. In particular, the sealing structure 4 does not necessarily include the rings R4, R4' resting on the connecting devices 1, 1' at the annular recess of the connecting devices 1, 1'. In some embodiments, an airtight joint near the channel 20 can be obtained by the housing unit 2 in continuous annular contact with the flexible material included in (or closely surrounding) the hose end 11a, provided that such contact is obtained around the intermediate portion 1c.

Claims

1. A sealing arrangement (100) for detecting a detectable gas in a hermetically sealed detection chamber (CH), the sealing arrangement (100) comprising: - Housing unit (2), the housing unit (2) is provided with a first housing part, a second housing part and an access channel (20), the first housing part and the second housing part defining the internal volume (V) of the housing unit (2) in the closed state; - A connecting device comprising a tubular portion extending from a first annular portion (101) to a second annular portion, the tubular portion having a fluid passage (8) and an annular intermediate portion (1c) located between the first annular portion and the second annular portion, the intermediate portion (1c) being arranged around the fluid passage (8); and - Sealing structure (4), the sealing structure (4) is adapted such that when the second annular portion is received in the internal volume (V) of the housing unit (2) in the closed state, the sealing structure (4) forms an airtight joint at the approach channel (20) by continuous contact around the intermediate portion (1c); The first annular portion (101) is configured such that when the flexible hose end (11a) is connected to the first annular portion (101) in an engaged state, the flexible hose end (11a) surrounds the first annular portion (101), and the second annular portion is provided with an attachment member, and The housing unit (2) is configured to receive the attachment member in the internal volume (V) such that gas escaping from the fluid passage (8) via at least one gas-permeable end (1b) included in the attachment member is hermetically held in the internal volume (V).

2. The sealing arrangement according to claim 1, wherein, The sealing structure (4) includes at least one member sandwiched between a first rigid member and a second rigid member, wherein the first rigid member forms all or part of the first housing portion and the second rigid member forms all or part of the second housing portion.

3. The sealing arrangement according to claim 1 or 2, wherein, The sealing structure (4) is elastically deformable, and the sealing arrangement (100) further includes a clamping member (23) disposed around the periphery of the housing unit (2) and surrounding the internal volume (V) for maintaining the compression state of the sealing structure (4) by locking the housing unit (2) in the closed state.

4. The sealing arrangement according to claim 1 or 2, wherein, The sealing structure (4) includes two deformable elements (4a, 4b), each of which is made of an elastic plastic material.

5. The sealing arrangement according to claim 4, wherein, The two deformable elements (4a, 4b) of the sealing structure (4) include: - Two basic planar portions (J1, J2), which are parallel to each other and connected to each other in the closed state, and - A ring (R4; R4') that is complementary to the two planar portions (J1, J2) and surrounds and encloses the intermediate portion (1c).

6. The sealing arrangement according to claim 4, wherein, The sealing structure (4) is provided with rings (R4) distributed in the two deformable parts (4a, 4b).

7. The sealing arrangement according to claim 1 or 2, wherein, The first annular portion (101) is a barbed nozzle made of plastic.

8. The sealing arrangement according to claim 1 or 2, wherein, The connecting device (1; 1') is provided with an annular recess, the intermediate portion (1c) extends in the annular recess, and the sealing structure (4) extends in the annular recess to surround the intermediate portion (1c).

9. The sealing arrangement according to claim 1 or 2, wherein, The first housing portion and the second housing portion are made of or comprise metal material.

10. The sealing arrangement according to claim 1 or 2, wherein, In the closed state of the housing unit (2), fluid communication between the internal volume (V) and the outside of the housing unit (2) can only be achieved via the fluid passage (8).

11. The sealing arrangement according to claim 1 or 2, wherein, The at least one gas-permeable end (1b) included in the attachment member includes an end opening (O'), the end opening (O'): - Belongs to the second annular portion; and - Covered by a gas-permeable membrane (36).

12. The sealing arrangement according to claim 1 or 2, comprising: - Flexible hose (11), which includes the flexible hose end (11a) surrounding and thus overlapping the first annular portion (101). - A clamping collar (48) is configured to permanently deformably press against the overlapping portion of the flexible hose end (11a) and the shank (46) of the first annular portion (101) with barbs, the shank (46) extending between the shoulder or adjacent portion (BP) and the barb (B) of the first annular portion (101).

13. The sealing arrangement according to claim 1 or 2, wherein, The housing unit (2) is provided with a connector fitting (51) having a connecting pipe (50) outside the fluid passage (8) that leads into the internal volume (V).

14. A method for monitoring leakage of a fluid transfer assembly (200) for fluid communication between two fluid receiving portions by using a sealing arrangement (100) according to claim 1, the method comprising: During the preparation stage: - Connect the connecting device to the hose (11) to obtain the connection state of the fluid transfer assembly (200), the connecting device forming the first fluid receiving portion of the two fluid receiving portions, the connection including: inserting the first annular portion (101) as the male portion into the hose (11) at the end (11a) of the flexible hose formed as the female portion, the hose (11) forming all or part of the second fluid receiving portion of the two fluid receiving portions; - An annular contact area (SC) is defined at the connection area where the flexible hose end (11a) overlaps the first annular portion (101). - Assemble the sealing arrangement (100) such that the fluid passage (8) communicates with the internal volume (V) of the housing unit (2) via an opening (O') covered by a gas-permeable membrane (36); And then, during the testing phase: - The tracer gas is injected into the accumulation space separated from the detection space by the annular contact area (SC) so as to accumulate the tracer gas in the fluid passage (8), the detection space being located in the hermetically sealed detection chamber (CH); Thus, any escape of tracer gas through a possible defect in the annular contact area (SC) can be detected in the detection space by a tracer gas sensor device (9) in fluid communication with the detection space.

15. The method according to claim 14, wherein, The fluid transfer assembly (200) is used in the biopharmaceutical assembly (18).

16. An apparatus for detecting a detectable gas in a hermetically sealed detection chamber (CH), the apparatus comprising: - A sterile container for positioning in the detection chamber (CH), the container having a flexible body that at least partially defines an internal chamber (42) for receiving and holding the detectable gas without leakage; - The sealing arrangement (100) according to claim 1, wherein the sealing arrangement is positioned in the detection chamber (CH); - A hose (11), the hose including a flexible hose end (11a) connected to the first annular portion (101) and allowing fluid communication between the at least one gas-permeable end (1b) and the internal chamber (42); - A sensor device (9) associated with the detection chamber (CH) and capable of sensing the detectable gas outside the inner chamber (42) in the detection space of the detection chamber (CH) due to leakage; and - A pumping assembly for generating a pressure differential between the internal chamber (42) and the detection chamber (CH); The housing unit (2) and the sealing structure (4) hermetically separate the internal volume (V) from the detection space, and the attachment member having at least one gas-permeable end (1b) is received in the internal volume (V).

17. The device of claim 16, comprising a detectable gas source (14) and a valve (V5) associated with said detectable gas source. The connecting device and the flexible hose end (11a) are connected at the coupling area to form a fluid transfer assembly (200), and The internal chamber (42) is configured such that when the valve (V5) is in the open state, the internal chamber is filled with the detectable gas via an injection line (L), and the injection line (L) is connected to the fluid passage (8) via the internal chamber (42).

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