Bag containing a biopharmaceutical product and probe holder port for such a product

Abstract

A bag (11) suitable for containing a biopharmaceutical product, said bag (11) comprising: - a flexible plastic casing (12) provided with at least one biopharmaceutical fluid input / output port (13) and a measurement opening (14) remote from the biopharmaceutical fluid input / output port (13), a first fastening zone (15) surrounding said at least one measurement opening (14); - a probe holder port (16) produced in the form of a thin part, the probe holder port (16) comprising a body (17) provided with an axial through-bore (18) and a peripheral collar (19) comprising a second fastening zone (20) and defining a fastening plane (21), the body (17) extending from a side outside the flexible plastic casing (12) relative to the fastening plane (21), the first and second fastening zones (15, 20) being sealably assembled together by bonding or welding; - a contact probe (22), extending in the axial through-bore (18), being sealably assembled on the probe holder port (16), the contact probe (22) comprising an active measurement end portion (23) disposed in contact with the biopharmaceutical product when the bag (11) is filled therewith, and an end portion (24) opposite the active measurement end portion (23), the probe holder port (16) comprising a transition portion (25) between the body (17) and the peripheral collar (19), extending between a radially central end portion (26) of the peripheral collar (19) and a first axial end portion of the body (17), the first axial end portion (27) of the body being the axial end portion of the body that is closest to the radially central end portion (26) of the peripheral collar (19), the first axial end portion (27) of the body being disposed on the outer side relative to the fastening plane (21), the active measurement end portion (23) being axially disposed on the outer side relative to the fastening plane (21).

Description

[0001] The invention relates to a bag containing a biopharmaceutical product and a probe port for such a product. The invention also relates to an assembly for containing a biopharmaceutical product, comprising a bag and a probe port. Finally, the invention relates to an assembly for measuring a biopharmaceutical product, the assembly comprising, on the one hand, a container for a biopharmaceutical product, including a bag and a probe port, and on the other hand, a contact probe.

[0002] The term "biopharmaceutical product" here refers to a product derived from biotechnology, such as culture media, cell cultures, buffer solutions, artificial nutrition fluids, or a pharmaceutical product, or more generally, a product intended for use in the medical field. Such a product is in liquid, paste, or powder form, in one or more phases, homogeneous or not, capable of flowing through a valve, and can thus be described as a fluid. The invention also applies to products other than biopharmaceuticals, as defined above, but which are subject to similar requirements regarding their storage or handling. In addition to transferring a biopharmaceutical product, the bag can be adapted for use in a bioreactor or fermenter.

[0003] The contact probe in this case refers to a probe for measuring parameters relating to the contents of the bag, such as pressure, pH, temperature, colorimetry, conductimetry, etc.

[0004] In the field of biopharmaceuticals, bags are commonly used as a site for carrying out chemical or biological reactions, and where applicable, for monitoring and / or controlling them, or even as a means of storage. To prevent the penetration of germs into the bag, it is essential that the environment be closed, sterile, and aseptic, without contact with the external environment.

[0005] The reactions must generally take place under specific and controlled conditions (pressure, pH, temperature, colorimetry, conductivity, etc.), or storage must be carried out under controlled conditions. It is therefore necessary to perform, more or less frequently, checks or measurements of parameters characterizing the product contained in the bag. These measurements must be performed under aseptic conditions, for the reasons mentioned above.

[0006] To perform these measurements, it is known to use a sensor device. The sensor device can consist, for example, of a probe. For this purpose, document WO 2013 / 083759 A1 discloses a probe as a sensor device. The probe disclosed in this document is a dry-storage probe. In this case, it is not necessary to store the probe in a buffer solution, such as potassium chloride. A dry-storage probe thus has the advantage of being easily stored, without the constraints of a buffer solution. This dry storage characteristic is particularly advantageous. In particular, it allows the entire assembly, consisting of the bag and the probe, to be stored without a buffer solution. More precisely, the bag does not require a buffer solution once the probe is attached to it. However, handling this type of probe is delicate.In particular, during assembly of the probe with the bag, the measuring tip of the probe, intended for direct contact with the biopharmaceutical product filling the bag, can be easily damaged. The same applies during transport or use of the probe and bag assembly. US2014 / 124504 A1 proposes a leak-proof connection device for an accessory receptacle, the active proximal portion of which is intended to be connected to the inside of the receptacle via an opening in the receptacle.The device comprises a first element, a second element and a chamber, the first element comprising a proximal end part which is fixed by sliding in the proximal direction, with insertion of a lateral sealing piece, on a complementary part of the receptacle, in the proximal direction, the transverse head corresponding to the lower face of the first element and being provided with a lateral head sealing element and the second element being able to be pre-assembled with the first element by axial sliding in the proximal direction.

[0007] One aim of the invention is to provide a pouch containing a biopharmaceutical product and a probe support port for such a product which does not have at least some of the disadvantages of prior art devices.

[0008] The invention relates to a pouch adapted to contain a biopharmaceutical product, said pouch comprising: a flexible plastic casing having at least one biopharmaceutical fluid inlet / outlet port and a measurement opening located away from the biopharmaceutical fluid inlet / outlet port, a first fixing zone surrounding said at least one measurement opening, a probe support port made in the form of a thin piece, the probe support port comprising a body having a through axial bore and a peripheral flange comprising a second fixing zone and defining a fixing plane, the body extending on one side outside the flexible plastic casing relative to the fixing plane, the first and second fixing zones being assembled together in a hermetic manner by gluing or welding, a contact probe extending in the through axial bore, being assembled to the probe support port in a hermetic manner,the contact probe comprising an active measuring tip portion disposed in contact with the biopharmaceutical product when the bag is filled, and a tip portion opposite the active measuring tip portion, the probe support port comprising a transition portion between the body and the peripheral collar, extending between a radially central end portion of the peripheral collar and a first axial end portion of the body, the first axial end portion of the body being the axial end portion of the body closest to the radially central end portion of the peripheral collar, the first axial end portion of the body being disposed on the outside relative to the fixing plane, the active measuring end portion being disposed axially on the outside relative to the fixing plane.

[0009] Thanks to these provisions, the active measuring tip portion of the probe is protected from damage that may occur during handling of the probe and / or the bag.

[0010] According to one embodiment, the transition portion is conical in shape, the diameter of the transition portion on the side of the peripheral collar being greater than the diameter on the side of the body.

[0011] According to one design, the height of the transition portion is between 5 mm and 20 mm.

[0012] According to one embodiment, the contact probe includes an intermediate portion between the active measuring end portion and the opposite end portion to the active measuring end portion, the intermediate portion comprising at least one O-ring being in tight contact with the axial bore through the body.

[0013] According to one embodiment, the contact probe is permanently assembled to the body of the probe support port.

[0014] According to one embodiment, the body comprises a second axial end portion, the second axial end portion of the body being opposite the first axial end portion of the body, and in which the end portion opposite the active end portion of the contact probe measurement has an external diameter equal to the external diameter of the second axial end portion of the body.

[0015] According to one embodiment, the external diameter of the intermediate part of the contact probe is less than the diameter of the end portion opposite the active measuring end portion of the contact probe.

[0016] According to one embodiment, the diameter of the axial bore through the body of the probe support port decreases from the second axial end portion of the body towards the first end portion of the body.

[0017] According to one embodiment, a locking element is disposed externally around the body and the end portion opposite the active measuring end portion of the contact probe.

[0018] According to one embodiment, the body includes on its external surface a circular stop for retaining the locking element, capable of cooperating with the locking element.

[0019] According to one embodiment, the locking element is cylindrical and hollow and includes a through axial bore whose axis coincides with the axis of the through axial bore of the body.

[0020] According to a second aspect, the invention relates to an assembly intended to contain a biopharmaceutical product, the assembly comprising a pouch and a probe support port, said pouch comprising a flexible plastic envelope having at least one biopharmaceutical fluid inlet / outlet port and a measurement opening distant from the biopharmaceutical fluid inlet / outlet port, a first fixation zone surrounding said at least one measurement opening, the probe support port being made in the form of a thin piece, the probe support port comprising a body having a through axial bore and a peripheral flange comprising a second fixation zone and defining a fixation plane, the body extending on one side outside the flexible plastic envelope relative to the fixation plane, the first and second fixation zones being assembled together in a leak-proof manner by gluing or welding, the probe support port comprising a transition portion between the body and the peripheral flange,extending between a radially central end portion of the peripheral collar and a first axial end portion of the body, the first axial end portion of the body being the axial end portion of the body closest to the radially central end portion of the peripheral collar, the first axial end portion of the body being disposed on the outside relative to the fixing plane, the active measuring end portion being disposed axially on the outside relative to the fixing plane.

[0021] We will now briefly describe the figures in the drawings. There figure 1 is an overview of a pouch containing a pharmaceutical product according to the invention. figure 2 is a perspective view of a probe support port according to the invention. figure 3 is a cross-sectional view of a probe support port and a contact probe according to the invention.

[0022] The following is a detailed description of several embodiments of the invention, accompanied by examples and references to drawings.

[0023] There figure 1 Figure 11 illustrates a pouch. Such a pouch 11 is suitable for containing a biopharmaceutical product. The pouch 11 comprises a flexible plastic envelope 12. The flexible plastic envelope 12 is provided with at least one inlet / outlet port 13 for the biopharmaceutical fluid. The pouch 11 further comprises a measuring aperture 14 and a first attachment zone 15 surrounding the measuring aperture 14. The measuring aperture 14 is intended for measuring various parameters of the biopharmaceutical product, such as, for example, the pH of the product. According to the invention, the measuring aperture 14 is located away from the inlet / outlet port 13. In other words, the measuring aperture 14 and the inlet / outlet port 13 are separate from each other.

[0024] As seen in more detail at the figure 2 , pocket 11 includes, at the measuring opening 14, a contact probe 22 and a probe support port 16.

[0025] The contact probe 22 is cylindrical in shape. The contact probe 22 is designed to measure a parameter of the biopharmaceutical product contained in the bag 11. For example, the contact probe 22 can be used to measure the pH of the product. Here, "contact probe" refers to a probe that requires physical contact with the product being measured (as opposed, for example, to an optical probe). It may also be possible to measure other parameters such as pressure, temperature, colorimetry, etc. The contact probe 22 comprises an active measuring end portion 23 and an opposing end portion 24. The opposing end portion 24 has an external diameter D24. For example, the external diameter D24 is between 21.5 mm and 27.5 mm. According to the example illustrated in the figure 2 The external diameter D24 is 24.5 mm. The active measuring tip portion 23 is positioned in contact with the biopharmaceutical product when the bag 11 is filled. The active measuring tip portion 23 includes, for example, two electrodes. For example, one of the two electrodes is standard and is called the reference electrode. The potential of this reference electrode is constant and known. The other of the two electrodes has a variable potential and is called the glass electrode. The potential of this glass electrode is a function of the pH. According to the example illustrated in particular in the figure 1 The two electrodes are separate. However, the two electrodes can be combined. When the contact probe 22 is assembled to the pouch 11, the active measuring end portion 23 is closer to the pouch 11 than the opposite end portion 24. The contact probe 22 further includes an intermediate portion 28. The intermediate portion 28 is arranged between the active measuring end portion 23 and the opposite end portion 24. The intermediate portion 28 has an external diameter D28. For example, the external diameter D28 is between 19.5 mm and 22.5 mm. According to the example illustrated in the figure 2 The external diameter D28 is 20.7 mm. Therefore, the external diameter D28 of the intermediate portion 28 is smaller than the external diameter D24 of the opposite end portion 24. Furthermore, according to the example illustrated in the figure 2 The intermediate portion 28 includes a bulge 29. In another example, the intermediate portion 28 may include several bulges 29. Furthermore, the intermediate portion 28 includes two circular grooves. The first circular groove is located on the side of the active measuring end portion 23 relative to the bulge 29, and the second circular groove is located on the side of the opposite end portion 24 relative to the bulge 29. Each circular groove receives an O-ring 38.

[0026] The probe support port 16 is made from a thin piece. For example, the thickness of the probe support port 16 varies between 1 mm and 3 mm. Furthermore, the probe support port 16 is injection molded.

[0027] As illustrated in figures 2 et 3 The probe support port 16 comprises a body 17, a transition portion 25 and a peripheral collar 19. The body 17 is generally cylindrical in shape. The body 17 includes a circular stop 32 on its outer surface. Furthermore, the body 17 is provided with a through axial bore 18. The through axial bore 18 is designed for the passage of the contact probe 22. The contact probe 22 is thus assembled to the body 17. In one example, the contact probe 22 is assembled to the body 17 by pouring resin between the contact probe 22 and the body 17. In another example, the contact probe 22 is press-fitted to the body 17. Consequently, it is difficult to separate the contact probe 22 from the probe support port 16 once the contact probe 22 is assembled with the body 17. The bulge 29 of the contact probe 22, as well as the O-rings 38, are in tight contact with the through axial bore 18.This axial bore 18 extends between a first axial end portion of the body 27 and a second axial end portion of the body 30. The first axial end portion of the body 27 is the axial end portion of the body closest to the active measuring end portion 23 of the contact probe 22 when the contact probe 22 is inserted into the probe holder port 16. The second axial end portion of the body 30 is opposite the first axial end portion of the body 17. Furthermore, the second axial end portion of the body 30 includes an external diameter D30. The external diameter D30 is identical to the diameter D24 of the opposite end portion 24 of the contact probe 22. Consequently, the external surfaces of the second axial end portion of the body 30 and the opposite end portion 24 of the contact probe 22 are flush. For example, the external diameter D30 is between 21.5 mm and 27.5 mm.According to the example illustrated in the . figure 2 The external diameter D30 is 24.5 mm. Furthermore, the axial bore 18 has a diameter D18. The diameter D18 is between 18 mm and 25 mm. More precisely, the diameter D18 is not constant along the entire length of the axial bore 18. In fact, the diameter D18 decreases from the second axial end portion of body 30 to the first axial end portion of body 27. For example, the difference measured between the two end portions 27 and 30 is 1.4 mm. According to another example, at a distance D of 30 mm, measured from the second axial end portion 30 to the first axial end portion 27, the surface of the through axial bore is inclined at 2.3° towards the second axial end portion 30. In addition, the surface of the through axial bore is inclined at 0.5° towards the first axial end portion 27.This decrease in size makes it easier to assemble the probe by contact 22 with the probe support port 16.

[0028] Furthermore, the peripheral flange 19 extends perpendicularly to the body 17. It comprises a first surface 19A and a second surface 19B. The first surface 19A is oriented towards the body 17. The second surface 19B is opposite the first surface 19A. In addition, the peripheral flange 19 includes a second mounting area 20. The second mounting area 20 defines a mounting plane 21. This second mounting area 20 is circular, with an external diameter D20 and an internal diameter D20'. The external diameter D20 is between 80 mm and 90 mm. For example, the external diameter D20 is 85 mm. The internal diameter D20' is between 52 mm and 57 mm. For example, the internal diameter D20' is 54.4 mm. The internal diameter D20' limits the radially central end portion 26 of the peripheral collar 19. According to an example illustrated in the figure 2 The second fixation zone 20 corresponds to the first surface 19A. According to another example, not shown, the second fixation zone 20 could correspond to the second surface 19B. Furthermore, the second fixation zone 20 is intended to be in contact with the first fixation zone 15 of the pouch 11. The first and second fixation zones 15, 20 are joined together in a hermetic manner. For example, the first and second fixation zones 15, 20 are joined together by gluing or welding. Preferably, the assembly between the first and second fixation zones 15, 20 is done by welding. Unlike gluing, welding avoids the potential for contamination within the pouch 11 due to the adhesive. According to the example illustrated in the figure 2 The flexible plastic casing 12 is welded to the first surface 19A of the collar 19. The probe support port 16 is thus firmly and securely attached to the pouch 11. Once the probe support port 16 is assembled to the pouch 11, the attachment plane 21 defines an exterior side and an interior side of the pouch 11. Consequently, the biopharmaceutical product in the pouch 11 extends on the interior side relative to the attachment plane 21, while the probe support port 16 extends on the exterior side relative to the attachment plane 21. This extension is complete when the second attachment zone 20 corresponds to the second surface 19B, or almost complete when the second attachment zone 20 corresponds to the first surface 19A.

[0029] The transition portion 25 is located between the body 17 of the probe support port 16 and the peripheral flange 19. More precisely, the transition portion 25 extends between the radially central end portion 26 of the peripheral flange 19 and the first axial end portion of the body 27. As can be seen in figures 2 et 3 This transition portion 25 is conical in shape. A conical shape has the advantage of avoiding sharp edges, which could damage the flexible plastic casing 12 of the bag 11. Furthermore, the transition portion 27 is sized to allow good circulation of the biopharmaceutical product within the conical section. Good circulation of the pharmaceutical product thus prevents distortion of the measurements taken by the contact probe 22. The diameter of the transition portion 25 is larger on the side of the fixation plane 21 than on the side of the first axial end portion of the body 27.Furthermore, the shape of the transition portion 27 protects the contact probe 22 from various forms of damage it might sustain, particularly during transport or use of the pouch 11, or during the assembly of the contact probe 22 to the pouch 11, the pouch 11 being pre-equipped with the probe support port 16. In addition, the height H25 of the transition portion 25 is between 5 mm and 20 mm. For example, the height H25 is between 9.7 mm and 10.3 mm. In another example, the height H25 is 10 mm. The height H25 is measured between plane 21 and the first axial end portion of body 27, at the level of the axial bore 18. The first axial end portion of body 27 is therefore distant from plane 21. Consequently, the active measuring end portion 23 of the contact probe 22 is distant from plane 21. The height H25 thus allows the active measuring portion 23 to be moved away from plane 21.Due to the shape of the transition portion 25, it is not necessary to add a protective element around the contact probe 22 to protect it from damage. The probe support port 16 therefore protects the contact probe 22 while maintaining a simple configuration. Furthermore, the probe support port 16 facilitates the mounting of the probe by contact 22 and also protects it during the assembly step of the probe by contact 22 in the probe support port 16. Indeed, the probe support port 16 is pre-assembled to the pocket 11. For example, the probe support port 16 is inserted into the pocket 11. Then, the probe support port 16 is passed through the measuring opening 14. Thus, the body 17 and the transition portion 25 extend from the outside of the pocket 11 and the collar extends from the inside of the pocket 11. The first and second fixing zones 15, 20 are then assembled together.The operator then places the pouch 11 flat on a hard surface, such as a table, ensuring that the flange 19 is flat against the surface. The operator then inserts the contact probe 22 into the probe holder port 16. The specific shape of the probe holder port 16 prevents the measuring tip 23 of the contact probe 22 from being damaged by contact with the flexible plastic sleeve 12 of the pouch 11 resting on the surface. Therefore, the operator can apply slightly more force than is required to insert the contact probe 22 into the probe holder port 16 without risking damage to the probe. The assembly operation is thus safer and easier for the operator, who does not need to exercise any particular vigilance. This assembly operation is also faster and therefore contributes to improved production of the pouch 11.

[0030] Furthermore, as can be seen at the figure 2The pocket 11 includes a locking element 31. The locking element 31 contributes to the assembly of the contact probe 22 with the probe support port 16. For example, the locking element 31 is held by elastic compression around the body 17 of the probe support port 16. The locking element 31 comprises a cylindrical portion 33, a first end portion 34, and a second end portion 35. The locking element 31 is arranged externally around the body 17 and the end portion 24 opposite the active measuring end portion 23 of the contact probe 22. More specifically, the cylindrical portion 33 surrounds the body 17 and the end portion 24. More specifically, the cylindrical portion 33 includes a through axial bore 36. The axis of the through axial bore 36 coincides with the axis of the through axial bore. 18 of the body 17. The cylindrical portion 33 further includes an internal diameter D33.

[0031] The first end portion 34 extends radially to the cylindrical portion 33. The first end portion 34 is in contact with the opposite end portion 24 of the contact probe 22. The first end portion 34 further includes an opening 37. The opening 37 is suitable for allowing the passage of the connecting elements associated with the contact probe 22. The second end portion 35 extends radially to the cylindrical portion 33. The second end portion 35 cooperates with the circular stop 32 of the body 17 of the probe support port 16. The circular stop 32 holds the locking element 31 in position around the contact probe 22 and the probe support port 16.

Claims

1. A bag (11) suitable for containing a biopharmaceutical product, said bag (11) comprising: - a flexible plastic sheath (12) provided with at least one biopharmaceutical fluid input / output port (13) and a measurement opening (14) remote from the biopharmaceutical fluid input / output port (13), a first fastening zone (15) surrounding said at least one measurement opening (14), - a probe holder port (16) produced in the form of a thin part, the probe holder port (16) comprising a body (17) provided with an axial through-bore (18) and a peripheral flange (19) comprising a second fastening zone (20) and defining a fastening plane (21), the body (17) extending from a side outside the flexible plastic sheath (12) relative to the fastening plane (21), the first and second fastening zones (15, 20) being sealingly assembled together by bonding or welding; - a contact probe (22) extending in the axial through-bore (18), being sealingly assembled on the probe holder port (16), the contact probe (22) comprising an active measurement end portion (23) disposed in contact with the biopharmaceutical product when the bag (11) is filled therewith, and an end portion (24) opposite the active measurement end portion (23), the probe holder port (16) comprising a transition portion (25) between the body (17) and the peripheral flange (19), the transition portion extending between a radially central end portion (26) of the peripheral flange (19) and a first axial end portion of the body (17), the first axial end portion (27) of the body being the axial end portion of the body that is closest to the radially central end portion (26) of the peripheral flange (19), the first axial end portion (27) of the body being disposed on the outer side relative to the fastening plane (21), the active measurement end portion (23) being axially disposed on the outer side relative to the fastening plane (21).

2. The bag (11) according to the preceding claim, wherein the transition portion (25) is conical, the diameter of the transition portion on the side with the peripheral flange (19) being greater than the diameter on the side with the body (17).

3. The bag (11) according to the preceding claim, wherein, the height (H25) of the transition portion (25) is between 5 mm and 20 mm.

4. The bag (11) according to any one of the preceding claims, wherein the contact probe (22) comprises an intermediate part (28) between the active measurement end portion (23) and the end portion (24) opposite the active measurement end portion, the intermediate portion (28) comprising at least one O-ring (38) being in sealing contact with the axial through-bore (18) of the body (17).

5. The bag (11) according to any one of the preceding claims, wherein the contact probe (22) is assembled with the body (17) of the probe holder port (16) in a permanent manner.

6. The bag (11) according to the preceding claim, wherein the body (17) comprises a second axial end portion (30), the second axial end portion (30) of the body being opposite the first axial end portion (27) of the body, and wherein the end portion (24) opposite the active measurement end portion (23) of the contact probe (22) has an external diameter (D24) that is equal to the external diameter (D30) of the second axial end portion (30) of the body (17).

7. The bag (11) according to the preceding claim, wherein the external diameter (D28) of the intermediate part (28) of the contact probe (22) is less than the diameter (D24) of the end portion (24) opposite the active measurement end portion (23) of the contact probe (22).

8. The bag (11) according to any one of the preceding claims, wherein the diameter of the axial through-bore of the body (17) of the probe holder port (16) decreases from the second axial end portion (30) of the body (17) towards the first end portion (27) of the body.

9. The bag (11) according to any one of the preceding claims, wherein a locking element (31) is disposed externally around the body (17) and the end portion (24) opposite the active measurement end portion (23) of the contact probe (22).

10. The bag (11) according to the preceding claim, wherein the body (17) comprises, on the external surface thereof, a circular abutment (32) for retaining the locking element (31), capable of interacting with the locking element (31).

11. The bag (11) according to the preceding claim, wherein the locking element (31) is cylindrical and hollow, and comprises an axial through-bore, the axis of which is coincident with the axis of the axial through-bore (18) of the body (17).

Images