BAG CONTAINING A BIOPHARMACEUTICAL PRODUCT AND PROBE SUPPORT PORT FOR SUCH A PRODUCT
The flexible plastic envelope with a conical transition portion and sealed assembly design addresses probe damage issues in biopharmaceutical bags, ensuring aseptic handling and easy assembly while maintaining measurement integrity.
Patent Information
- Application Number
- FR2017071039
- Authority / Receiving Office
- FR · FR
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2017-10-02
- Publication Date
- 2025-10-03
- Estimated Expiration
- 2037-10-02
AI Technical Summary
Existing biopharmaceutical product bags with integrated probes face issues of probe damage during handling, assembly, and transport due to the need for aseptic conditions and the use of dry-storable probes without buffer solutions.
A flexible plastic envelope with a probe support port featuring a conical transition portion and a sealed assembly design protects the active measuring end of the probe, ensuring aseptic handling and easy assembly.
The solution effectively safeguards the probe from damage and facilitates aseptic measurement operations, enhancing the assembly process and maintaining measurement integrity.
Smart Images
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Abstract
Description
The invention relates to a bag containing a biopharmaceutical product and a probe support port for such a product. The invention also relates to an assembly intended to contain a biopharmaceutical product, comprising a bag and a probe support port. Finally, the invention relates to an assembly intended to measure a biopharmaceutical product, the assembly comprising on the one hand an assembly intended to contain a biopharmaceutical product, comprising a bag and a probe support port, and on the other hand a contact probe. Here, the term "biopharmaceutical product" is understood to mean a product derived from biotechnology, such as culture media, cell cultures, buffer solutions, artificial nutrition liquids, or a pharmaceutical product or more generally a product intended for use in the medical field. Such a product is in liquid, pasty, powdery form, in one or more phases, homogeneous or not, capable of flowing through a valve, thus being able to be described as a fluid. The invention also applies to products other than biopharmaceuticals, according to the definition just given, but which are subject to similar requirements with regard to their storage or processing. In addition to the transfer of a biopharmaceutical product, the bag can be adapted for a bioreactor or a fermenter. The contact probe in this case means a probe for measuring parameters relating to the contents of the bag, such as pressure, pH, temperature, colorimetry, conductimetry, etc. In the field of biopharmaceuticals, it is common to use bags as a place to carry out chemical or biological reactions, and if necessary to monitor and / or control them, or even as a means of storage. In order to prevent the penetration of germs inside the bag, it is important that the environment is closed, sterile and aseptic, without contact with the external environment. Reactions must, in general, take place under specific and controlled conditions (pressure, pH, temperature, colorimetry, conductimetry, etc.) or storage must be carried out under controlled conditions. It is therefore necessary to carry out more or less frequent checks or measurements of parameters characterizing the product contained in the bag. These measurements must be carried out under aseptic conditions, for the reasons indicated above. In order to carry out these measurements, it is known to use a sensor device. The sensor device may consist, for example, of a probe. For this purpose, document WO 2013 / 083759 A1 discloses a probe as a sensor device. The probe disclosed by this document is a dry storable probe. In this case, it is not necessary to store the probe in a buffer solution, such as potassium chloride. A dry-storable probe thus has the advantage of being easy to store, without the constraints of a buffer solution. This dry storage feature is particularly advantageous. In particular, it allows the assembly formed by the bag and the probe to be stored without a buffer solution. More precisely, the bag does not need to contain a buffer solution once the probe is assembled to the bag. However, handling this type of probe is delicate. In particular, when assembling the probe with the bag, the measuring end of the probe, intended to be in direct contact with the biopharmaceutical product filling the bag, can be easily damaged. The same is true during transport or use of the assembly formed by the probe and the bag. An aim of the invention is to propose a pocket containing a biopharmaceutical product and a probe support port for such a product which does not have at least some of the drawbacks of the devices of the prior art. According to a first aspect, the invention relates to a pocket suitable for containing a biopharmaceutical product, said pocket comprising: - a flexible plastic envelope provided with at least one biopharmaceutical fluid inlet / outlet port and a measuring opening distant from the biopharmaceutical fluid inlet / outlet port, a first fixing zone surrounding said at least one measuring opening, - a probe support port produced in the form of a thin piece, the probe support port comprising a body provided with an axial through bore and a peripheral collar comprising a second fixing zone and defining a fixing plane, the body extending on one side outside the flexible plastic envelope relative to the fixing plane, the first and second fixing zones being assembled together in a sealed manner by gluing or welding, - a contact probe extending into the axial through bore, being assembled to the probe support port in a sealed manner, the contact probe comprising an active measuring end portion arranged in contact with the biopharmaceutical product when the bag is filled therewith, and an end portion opposite the active measuring end 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 arranged on the outer side relative to the fixing plane, the active measurement end portion being arranged axially on the outer side relative to the fixing plane. Thanks to these provisions, the active measuring end portion of the probe is protected from damage that may occur when handling the probe and / or the bag. 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. According to one embodiment, the height of the transition portion is between 5 mm and 20 mm. According to one embodiment, the contact probe comprises an intermediate portion between the active measuring end portion and the end portion opposite the active measuring end portion, the intermediate portion comprising at least one O-ring being in sealed contact with the axial through bore of the body. In one embodiment, the contact probe is permanently assembled to the body of the probe support port. 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 measurement end portion of the contact probe has an external diameter equal to the external diameter of the second axial end portion of the body. 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. According to one embodiment, the diameter of the axial bore passing 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. According to one embodiment, a locking element is arranged externally around the body and the end portion opposite the active measuring end portion of the contact probe. According to one embodiment, the body comprises on its external surface a circular stop for holding the locking element, capable of cooperating with the locking element. According to one embodiment, the locking element is of cylindrical and hollow shape and comprises an axial through bore with an axis coincident with the axis of the axial through bore of the body. According to a second aspect, the invention relates to an assembly intended to contain a biopharmaceutical product, the assembly comprising a pocket and a probe support port, said pocket comprising a flexible plastic envelope provided with at least one biopharmaceutical fluid inlet / outlet port and a measuring opening distant from the biopharmaceutical fluid inlet / outlet port, a first fixing zone surrounding said at least one measuring opening, the probe support port being produced in the form of a thin piece, the probe support port comprising a body provided with an axial through bore and a peripheral collar comprising a second fixing zone and defining a fixing plane, the body extending on one side outside the flexible plastic envelope relative to the fixing plane, the first and second fixing zones being assembled together in a sealed manner by gluing or welding, 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 arranged on the outer side relative to the fixing plane, the active measurement end portion being arranged axially on the outer side relative to the fixing plane. The figures in the drawings are now briefly described. 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 sectional view of a probe support port and a contact probe according to the invention. Below is a detailed description of several embodiments of the invention with examples and reference to the drawings. Figure 1 illustrates a bag 11. Such a bag 11 is adapted to contain a biopharmaceutical product. The bag 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 bag 11 further comprises a measuring opening 14 and a first attachment zone 15 surrounding the measuring opening 14. The measuring opening 14 is provided to measure different parameters of the biopharmaceutical product, such as for example the pH of the product. According to the invention, the measuring opening 14 is distant from the inlet / outlet port 13. In other words, the measuring opening 14 and the inlet / outlet port 13 are distinct from each other. As seen in more detail in Figure 2, the pocket 11 comprises, at the measurement opening 14, a contact probe 22 and a probe support port 16. The contact probe 22 is cylindrical in shape. The contact probe 22 is intended to measure a parameter of the biopharmaceutical product contained in the bag 11. For example, the contact probe 22 makes it possible to measure the pH of the product. By "contact probe" is meant here a probe which requires physical contact with the product to be 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 opposite end portion 24. The opposite end portion 24 comprises 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 FIG. 2, the external diameter D24 is 24.5 mm. The active measuring end portion 23 is arranged in contact with the biopharmaceutical product when the pocket 11 is filled with it.The active measuring end portion 23 comprises, for example, two electrodes. For example, one of the two electrodes is standard and 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 FIG. 1, the two electrodes are separate. However, the two electrodes can be combined. When the contact probe 22 is assembled to the bag 11, the active measuring end portion 23 is closer to the bag 11 than the opposite end portion 24. The contact probe 22 further comprises 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 comprises an external diameter D28.For example, the outer diameter D28 is between 19.5 mm and 22.5 mm. According to the example illustrated in Figure 2, the outer diameter D28 is 20.7 mm. The outer diameter D28 of the intermediate portion 28 is therefore less than the outer diameter D24 of the opposite end portion 24. Furthermore, according to the example illustrated in Figure 2, the intermediate portion 28 comprises a bulge 29. According to another example, the intermediate portion 28 may comprise several bulges 29. In addition, the intermediate portion 28 comprises two circular grooves. The first circular groove is arranged on the side of the active measuring end portion 23 with respect to the bulge 29, and the second circular groove is arranged on the side of the opposite end portion 24 with respect to the bulge 29. Each circular groove receives an O-ring 38. The probe support port 16 is made as a thin piece. For example, the thickness of the probe support port 16 varies between 1 mm and 3 mm. In addition, the probe support port 16 is made by injection molding. As illustrated in Figures 2 and 3, the probe support port 16 comprises a body 17, a transition portion 25 and a peripheral flange 19. The body 17 is generally cylindrical in shape. The body 17 comprises on its external surface a circular stop 32. In addition, the body 17 is provided with an axial through bore 18. The axial through bore 18 is provided for the passage of the contact probe 22. The contact probe 22 is thus assembled to the body 17. According to one example, the contact probe 22 is assembled to the body 17 by casting a resin between the contact probe 22 and the body 17. According to another example, the contact probe 22 is force-fitted to the body 17. As a result, it is difficult to separate the contact probe 22 from the probe support port 16 once the contact probe 22 is fitted to the body 17. The bulge 29 of the contact probe 22 and the O-rings 38 are in sealing contact with the axial through bore 18. This axial through 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 support 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 comprises an outer diameter D30. The outer diameter D30 is identical to the diameter D24 of the opposite end portion 24 of the contact probe 22. As a result, the outer 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 outer diameter D30 is between 21.5 mm and 27.5 mm. According to the example illustrated in FIG. 2, the outer diameter D30 is 24.5 mm. Furthermore, the axial through bore 18 comprises a diameter D18. The diameter D18 is between 18 mm and 25 mm. More precisely, the diameter D18 is not constant over the entire length of the axial through bore 18. Indeed, the diameter D18 decreases from the second axial end portion of the body 30 towards the first axial end portion of the body 27.For example, the measured gap 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 axial through bore is inclined by 2.3" toward the second axial end portion 30. Furthermore, the surface of the axial through bore is inclined by 0.5" toward the first axial end portion 27. This decrease in particular facilitates the assembly of the contact probe 22 with the probe support port 16. Furthermore, the peripheral collar 19 extends perpendicularly relative 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. Furthermore, the peripheral collar 19 comprises a second fixing zone 20. The second fixing zone 20 defines a fixing plane 21. This second fixing zone 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 FIG. 2, the second fixing zone 20 corresponds to the first surface 19A.According to another example, not illustrated, the second fixing zone 20 may correspond to the second surface 19B. Furthermore, the second fixing zone 20 is intended to be in contact with the first fixing zone 15 of the pocket 11. The first and second fixing zones 15, 20 are assembled together in a sealed manner. For example, the . first and second fixing zones 15, 20 are assembled together by gluing or welding. Preferably, the assembly between the first and second fixing zones 15, 20 is done by welding. Unlike gluing, welding makes it possible not to potentially cause contamination within the pocket 11 due to the adhesive agent. According to the example illustrated in FIG. 2, the flexible plastic envelope 12 is welded to the first surface 19A of the collar 19. The probe support port 16 is thus firmly fixed to the pocket 11, and in a sealed manner. Once the probe support port 16 is assembled to the pocket 11, the fixing plane 21 defines a side outside the pocket 11 and an inside side.Therefore, the biopharmaceutical product present in the pocket 11 extends on the inner side relative to the fixing plane 21 while the probe support port 16 extends on the outer side relative to the fixing plane 21, in its entirety when the second fixing zone 20 corresponds to the second surface 19B, or in its almost entirety when the second fixing zone 20 corresponds to the first surface 19A. The transition portion 25 is disposed between the body 17 of the probe support port 16 and the peripheral collar 19. More specifically, the transition portion 25 extends between the radially central end portion 26 of the peripheral collar 19 and the first axial end portion of the body 27. As can be seen in FIGS. 2 and 3, this transition portion 25 is conical in shape. A conical shape has the advantage of avoiding sharp edges, which could cause damage to the flexible plastic casing 12 of the pouch 11. Furthermore, the transition portion 27 is sized to allow good circulation of the biopharmaceutical product inside the conical-shaped portion. Good circulation of the pharmaceutical product thus makes it possible not to distort the measurements taken by the contact probe 22.The diameter of the transition portion 25 is larger on the side of the fixing plane 21 than on the side of the first axial end portion of the body 27. Furthermore, the shape of the transition portion 27 makes it possible to protect the contact probe 22 from the various damages that it could undergo, in particular due to the transport or use of the pocket 11 or during the step of assembling the contact probe 22 to the pocket 11, the pocket 11 being previously provided with the probe support port 16. Furthermore, 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. According to another example, the height H25 is 10 mm. The height H25 is measured between the plane 21 and the first axial end portion of the body 27, at the level of the axial through bore 18. The first axial end portion of the body 27 is therefore distant from the plane 21.As a result, the active measurement end portion 23 of the contact probe 22 is distant from the plane 21. The height H25 therefore makes it possible to move the active measurement portion 23 away from the 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 in order to protect it from any damage. The probe support port 16 therefore makes it possible to protect the contact probe 22 while maintaining a simple configuration. In addition, the probe support port 16 makes it easier to mount the contact probe 22 and also to protect it during the step of assembling the contact probe 22 in the probe support port 16. Indeed, the probe support port 16 is previously 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 on the outer side of the pocket 11 and the flange extends on the inner side of the pocket 11. The first and second fixing zones 15, 20 are then assembled together. The operator then places the pocket 11 flat on a hard support, for example a table, ensuring that the flange 19 is laid flat relative to the support. The operator then inserts the contact probe 22 into the probe support port 16. The dedicated shape of the probe support port 16 prevents the measuring end 23 of the contact probe 22 from being damaged by contact with the flexible plastic casing 12 of the pocket 11 opposite resting on the support.Thus the operator can exert a force slightly greater than that required to insert the contact probe 22 into the probe support port 16 without risking damaging the latter. The assembly operation is in fact safe and easier for the operator who does not have to be particularly vigilant. This assembly operation is then also in fact faster and thus contributes to improving the production of the pocket 11. Furthermore, as seen in Figure 2, the pocket 11 comprises 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 fitting 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 measurement end portion 23 of the contact probe 22. More precisely, the cylindrical portion 33 surrounds the body 17 and the end portion 24. More precisely, the cylindrical portion 33 comprises an axial through bore 36. The axis of the axial through bore 36 coincides with the axis of the axial bore 18 passing through the body 17.The cylindrical portion 33 further comprises an internal diameter D33. The first end portion 34 extends radially to the cylindrical portion 33. The first end portion 34 is arranged in contact with the opposite end portion 24 of the contact probe 22. The first end portion 34 further comprises an opening 37. The opening 37 is capable of allowing the connection elements connected to the contact probe 22 to pass through. 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. The invention is not limited to the examples described above but is susceptible to numerous variants accessible to those skilled in the art. For example, although the above description refers to a probe by contact, the probe support port can be adapted to any measuring device such as optical sensors, temperature sensors, pressure sensors.
Claims
Claims 1. Pouch (11) adapted to contain a biopharmaceutical product, said pouch (11) comprising: - a flexible plastic envelope (12) provided with at least one inlet / outlet port (13) for biopharmaceutical fluid and a measuring opening (14) distant from the inlet / outlet port (13) for biopharmaceutical fluid, a first fixing zone (15) surrounding said at least one measuring opening (14), - a probe support port (16) produced in the form of a thin piece, the probe support port (16) comprising a body (17) provided with an axial through bore (18) and a peripheral collar (19) comprising a second fixing zone (20) and defining a fixing plane (21), the body (17) extending on one side outside the flexible plastic envelope (12) relative to the fixing plane (21), the first and second fixing zones (15, 20) being assembled together in a sealed manner by gluing or welding, - a contact probe (22) extending into the axial through bore (18), being assembled to the probe support port (16) in a sealed manner, the contact probe (22) being locked with the probe support port (16), the contact probe (22) comprising an active measuring end portion (23) arranged in contact with the biopharmaceutical product when the bag (11) is filled therewith, and an opposite end portion (24) to the active measuring end portion (23), Characterized in that the probe support port (16) comprises 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 of the body (27) being the axial end portion of the body closest to the radially central end portion (26) of the peripheral collar (19), the first axial end portion of the body (27) being arranged on the outer side relative to the fixing plane (21), the active measurement end portion (23) being arranged axially on the outer side relative to the fixing plane (21).
2. Pouch (11) according to the preceding claim, in which the transition portion (25) is conical in shape, the diameter of the transition portion on the side of the peripheral collar (19) being greater than the diameter on the side of the body (17).
3. Pocket (11) according to the preceding claim, in which the height (H25) of the transition portion (25) is between 5 mm and 20 mm.
4. Pouch (11) according to any one of the preceding claims, wherein the contact probe (22) comprises an intermediate portion (28) between the active measuring end portion (23) and the opposite end portion (24) to the active measuring 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. A pouch (11) according to any preceding claim, wherein the contact probe (22) is permanently attached to the body (17) of the probe support port (16).
6. Pouch (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 of the body (27), and wherein the end portion (24) opposite the active measuring end portion (23) of the contact probe (22) has an external diameter (D24) equal to the external diameter (D30) of the second axial end portion (30) of the body (16).
7. Pouch (11) according to the preceding claim, wherein the external diameter (D28) of the intermediate portion (28) of the contact probe (22) is less than the diameter (D24) of the end portion (24) opposite the active measuring end portion (23) of the contact probe (22).
8. A pouch (11) according to any preceding claim, wherein the diameter of the axial bore through the body (17) of the probe support port (16) decreases from the second axial end portion (30) of the body (17) towards the first end portion of the body (27).
9. A pouch (11) according to any preceding claim, wherein a locking member (31) is disposed externally around the body (16) and the opposite end portion (24) to the active measuring end portion (23) of the contact probe (22).
10. Pouch (11) according to the preceding claim, in which the body (17) comprises on its external surface a circular stop (32) for holding the locking element (31), capable of cooperating with the locking element (31).
11. Pouch (11) according to the preceding claim, in which the locking element (31) is of cylindrical and hollow shape and comprises an axial through bore with an axis coincident with the axis of the axial through bore (18) of the body (17).
12. Assembly intended to contain a biopharmaceutical product, the assembly comprising a pocket (11) and a probe support port (16), said pocket (11) comprising a flexible plastic envelope provided with at least one inlet / outlet port (13) for biopharmaceutical fluid and a measuring opening (14) distant from the inlet / outlet port (13) for biopharmaceutical fluid, a first fixing zone (15) surrounding said at least one measuring opening (14), the probe support port (16) being produced in the form of a thin piece, the probe support port (16) comprising a body (17) provided with an axial through bore (18) and a peripheral collar (19) comprising a second fixing zone (20) and defining a fixing plane (21), the body (17) extending 5 on an outside side of the flexible plastic envelope relative to the fixing plane (21), the first and second fixing zones (15, 20) being assembled together in a sealed manner by gluing or welding, Characterized in that the probe support port (16) comprises a transition portion (25) between the body (17) and the peripheral collar (19), the transition portion (25) being conical in shape and the diameter of the transition portion on the side of the peripheral collar (19) being greater than the diameter on the side of the body (17), 10 extending between a radially central end portion (26) of the peripheral collar (19) and a first axial end portion of the body (27), the first axial end portion of the body (27) being the axial end portion of the body closest to the radially central end portion (26) of the peripheral collar (19), the first axial end portion of the body (27) being arranged on the outer side relative to the fixing plane (21), the active measurement end portion (23) being arranged axially on the outer side relative to the fixing plane (21).