WO2018152561A1 - Procédé de contrôle de l'étanchéité d'un récipient flexible - Google Patents

Procédé de contrôle de l'étanchéité d'un récipient flexible Download PDF

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Publication number
WO2018152561A1
WO2018152561A1 PCT/AT2018/060050 AT2018060050W WO2018152561A1 WO 2018152561 A1 WO2018152561 A1 WO 2018152561A1 AT 2018060050 W AT2018060050 W AT 2018060050W WO 2018152561 A1 WO2018152561 A1 WO 2018152561A1
Authority
WO
WIPO (PCT)
Prior art keywords
container
gas
fluid
bag
pressure vessel
Prior art date
Application number
PCT/AT2018/060050
Other languages
German (de)
English (en)
Other versions
WO2018152561A8 (fr
Inventor
Thomas Wurm
Original Assignee
Mits Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from ATA50408/2017A external-priority patent/AT519682A1/de
Application filed by Mits Gmbh filed Critical Mits Gmbh
Priority to SG11201903073VA priority Critical patent/SG11201903073VA/en
Priority to EP18719739.7A priority patent/EP3500833B1/fr
Priority to CN201880004508.5A priority patent/CN109983316B/zh
Publication of WO2018152561A1 publication Critical patent/WO2018152561A1/fr
Priority to US16/374,020 priority patent/US11262268B2/en
Publication of WO2018152561A8 publication Critical patent/WO2018152561A8/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01M—TESTING STATIC OR DYNAMIC BALANCE OF MACHINES OR STRUCTURES; TESTING OF STRUCTURES OR APPARATUS, NOT OTHERWISE PROVIDED FOR
    • G01M3/00—Investigating fluid-tightness of structures
    • G01M3/02—Investigating fluid-tightness of structures by using fluid or vacuum
    • G01M3/04—Investigating fluid-tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point
    • G01M3/20—Investigating fluid-tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material
    • G01M3/22—Investigating fluid-tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material for pipes, cables or tubes; for pipe joints or seals; for valves; for welds; for containers, e.g. radiators
    • G01M3/226—Investigating fluid-tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material for pipes, cables or tubes; for pipe joints or seals; for valves; for welds; for containers, e.g. radiators for containers, e.g. radiators
    • G01M3/227—Investigating fluid-tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material for pipes, cables or tubes; for pipe joints or seals; for valves; for welds; for containers, e.g. radiators for containers, e.g. radiators for flexible or elastic containers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01M—TESTING STATIC OR DYNAMIC BALANCE OF MACHINES OR STRUCTURES; TESTING OF STRUCTURES OR APPARATUS, NOT OTHERWISE PROVIDED FOR
    • G01M3/00—Investigating fluid-tightness of structures
    • G01M3/02—Investigating fluid-tightness of structures by using fluid or vacuum
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01M—TESTING STATIC OR DYNAMIC BALANCE OF MACHINES OR STRUCTURES; TESTING OF STRUCTURES OR APPARATUS, NOT OTHERWISE PROVIDED FOR
    • G01M3/00—Investigating fluid-tightness of structures
    • G01M3/02—Investigating fluid-tightness of structures by using fluid or vacuum
    • G01M3/04—Investigating fluid-tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point
    • G01M3/20—Investigating fluid-tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material
    • G01M3/202—Investigating fluid-tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material using mass spectrometer detection systems

Definitions

  • the present invention relates to a method for checking a tightness of a flexible container for a fluid, in particular for a fluid medicament, as well as the flexible container for a fluid medicament itself.
  • Such flexible containers for fluid drugs can be used for example as so-called single-use bags to store and transport very high-quality, liquid biopharmaceuticals. They can be made as two edge-welded plastic layers - in particular plastic films - which are flexible ("flexible wall").
  • a two-stage verification method has therefore been established in the prior art in which an exact check is first carried out at the place of manufacture of the container and, secondly, a further check is carried out immediately before use (at the "point of use").
  • the check at the place of manufacture works so that helium is introduced into the container. It should be noted that this really only applies to the container itself. Any hoses, connectors, filters and the like will not be tested.
  • the helium-filled container is placed in a vacuum chamber. By evacuating the vacuum chamber and the detection of existing in the vacuum chamber
  • Tightness or the presence of a leak can be closed. This measurement is highly sensitive. Leaks with sizes less than 5 pm can be detected.
  • the container is at the same time heavily loaded, since by the admission 81627 32 / fr With helium a balloon-like unfolding and puffing of the container takes place.
  • this method of the prior art however, a greater accuracy at the place of use is not achieved, since corresponding devices for high vacuum and the like are not readily available.
  • a check is also carried out directly at the point of use, whereby the container is subjected to a relatively low pressure (about 30 millibar) and monitored for about half an hour If this is too much the case, then a leak can be inferred, but with this method, leaks that are 20 pm or less in size can not be detected.
  • the object of the invention is therefore to provide a method and a device which make it possible to reduce the risk of sterility of a flexible container for fluid medicaments and similar products, for example from the pharmaceutical production process.
  • this object is achieved with the features of claim 1.
  • the device this is done by the features of claim 10.
  • the container that is to say quasi the test item
  • the container is covered at least partially - preferably completely - with a gas-permeable layer
  • the container together with a gas-permeable layer in a flexible, substantially gastight bag (the emergence of smaller amounts of fluid after closing may be acceptable depending on the application),
  • the substantially gas-tight bag is evacuated by pumping through a bag opening
  • the container is filled with a noble gas
  • the vacuum chamber used in the prior art can be eliminated from the process.
  • the inflation of the container is prevented, thereby preventing the introduction of new damage, especially leaks prevented. Because by evacuating the gap between the container to be tested and the substantially gas-tight bag ultimately affects the ambient pressure (on the substantially gas-tight bag and the gas-permeable layer) on the flexible container from the outside.
  • the gas-permeable layer allows the migration of helium, which emerges from the container via a leak, by pumping from the substantially gas-tight bag to a detection device.
  • a gas-permeable layer may preferably be a non-woven or the like are used.
  • the gas-permeable layer may be made of plastic.
  • the method according to the invention has, on the one hand, the advantage of the required accuracy, since leakages with sizes of less than 3 to 5 ⁇ m can be detected, and, on the other hand, the flexible container to be tested is subjected to less mechanical stress, which increases the risk of leakages introduced by the check reduced.
  • the filling of the container with the noble gas can be done before, during or after the evacuation of the bag.
  • the object is achieved by a set of a flexible container for a fluid, in particular for a fluid medicament, and a gas pressure vessel for receiving a noble gas. Again, this reduces the need for expensive laboratory equipment at the inspection site, as appropriate noble gas is supplied directly with the flexible container.
  • prefabrication of the flexible container together with the gas pressure vessel also sources of error in performing the review can be eliminated, which can easily arise when filling the container with inert gas. For example, by applying too much pressure or improperly connecting an external pressure source to the container (for example, because terminals do not fit together sufficiently or the like).
  • the container has an opening which is substantially gastight (the leakage of smaller amounts of fluid after closing may be acceptable depending on the application) can be closed and which is designed so that it produces an outwardly gas-tight fluid connection between the container and the gas pressure vessel can be.
  • the bag may also be part of the kit according to the invention.
  • the invention it is also possible to test the container including attachments, such as hoses, connectors, valves and the like.
  • the container may for example consist of polyethylene, ethylene-vinyl acetate, fluoropolymers or mixtures thereof.
  • the filling of the container can, as mentioned, be done by the container is brought via an opening with a filled with the inert gas pressure vessel in - preferably gas-tight - fluid communication.
  • the gas pressure vessel before evacuation - preferably completely - are arranged within the substantially gas-tight bag.
  • the gas pressure vessel before evacuation - preferably completely - are arranged within the substantially gas-tight bag.
  • this allows a particularly simple process implementation.
  • the activation of the gas pressure vessel can thereby function contactlessly via any type of electromagnetic waves. Since the substantially gas-tight bag can also be flexible or elastic, the filling of the container with inert gas could also be triggered by a switch actuated by the bag on the gas pressure vessel.
  • Helium can preferably be used as inert gas, since it has the smallest molecular weight of the noble gases and therefore-insofar as this can be said to correspond to the corresponding size scales-has the smallest "dimensions.” As a result, the smallest possible holes or leaks can be detected in the container. because larger noble gas atoms might not pass through the corresponding holes).
  • the measurement accuracy may be beneficial if the substantially gas-tight bag is kept evacuated by constant pumping. That is, the pumping can be adjusted only when a representative signal from the detection device is present.
  • the pumping example pulsed or otherwise controlled or regulated, for example, to save energy.
  • mass spectrometers may be used as detectors to detect the presence of the noble gas exiting via the bag opening.
  • the fluid may preferably be a fluid drug.
  • the invention can also be used in similar valuable products, such as precursors of drugs and other substances that occur in the (bio) pharmaceutical production process, the tightness of the container is also important on very small scales.
  • the fluid may also preferably be a liquid. In a very preferred embodiment, the fluid may be a liquid drug.
  • the flexible container may be used, preferably once, to store and / or transport a fluid drug if no leak is detected during the check. Thereafter, the container can be disposed of. In this case, one speaks of so-called single-use bags. It may be beneficial to the measurement accuracy, if the process is carried out on a - preferably completely emptied container.
  • the method can be used particularly effectively in containers that are so flexible that they can be substantially completely emptied without the application of a negative pressure.
  • the gas pressure vessel can communicate with the vessel via the closable opening, preferably with a hose and / or pipe connection.
  • the gas pressure vessel is relatively small. This means, in particular, that its capacity is such that an amount of the noble gas that stores the gas pressure vessel, under normal conditions, that is, at ambient pressure, does not exceed twice the nominal capacity of the container. More preferably, the capacity may be such that this volume does not exceed the nominal capacity of the container, and more preferably three quarters and more preferably half of the nominal capacity.
  • Fig. 1 is a schematic representation of the experimental setup for the
  • FIGS. 2a and 2b are schematic illustrations of the set according to the invention and of the set according to the invention after covering with the gas-permeable layer. In one embodiment of the method according to the invention
  • helium is used as the noble gas.
  • the experimental setup is shown purely schematically in Fig. 1 and can be made so compact that the verification of the tightness at the place of filling the Container 2 can be reliably performed.
  • the container 2 is flexible and, for example, as shown schematically in Fig. 2a formed. This is at least partially - preferably completely - coated with the gas-permeable layer 3.
  • the container 2 is in the set with the gas pressure vessel 7.
  • the gas pressure vessel 7 is connected via a hose connection and the opening 6 on the container 2 to the container 2.
  • the opening 6 is closed gas-tight and indicated in Fig. 1 only schematically as a crossing point of the hose connection with the container 2.
  • the container 2 is completely encased by the gas-permeable layer 3, wherein the gas-permeable layer 3 is designed in this embodiment as a fleece.
  • the container 2 enclosed by the gas-permeable layer 3, together with the hose connection and the gas pressure container 7, are arranged in the substantially gas-tight bag 4.
  • the interior of the bag 4 is connected to the detector 8 via the bag opening 5 (also shown only schematically as an intersection between the bag 4 and a connection of the detector 8 to the bag 4).
  • the detector 8 also comprises a vacuum pump for evacuating the bag 4 as well as the complete, necessary hardware and software for detecting helium in the gas stream, which is produced by the evacuation.
  • the gas-permeable layer 3 reduces any destructive forces on the container 2 during evacuation. At the same time, the gas-permeable layer 3 allows the migration of helium emerging from a leak of the container 2 to the bag opening 5 even in the evacuated state of the outer bag 5 the leaked helium be pumped in the direction of the detector 8. In other words, prevents the gas-permeable layer 3 that the outer bag 4 seals any holes of the container 2 during evacuation.
  • the bag opening 5 may be present in the measurement setup in multiple execution (on the container 2), for example on opposite sides of the container 2. This may result in leaked helium paths as short as possible to the detector 8.
  • the container 2 must be filled with inert gas from the gas pressure vessel 7 before the detection. This can be either before, during or after the evacuation happen.
  • the opening 6 When filling after evacuation, the opening 6 must be opened accordingly, which, for example, can operate without contact by transmitting electromagnetic waves.
  • the gas pressure vessel 7 is dimensioned in this embodiment so that after opening the opening 6, the noble gas (helium) occupies about half of the nominal volume of the container 2 (at about 1 bar ambient pressure). (This results in a differential pressure between the interior of the container 2 and the gap between the container 2 and the substantially gas-tight bag 4 of about 1 bar, since the gap is indeed evacuated.)
  • FIG. 2a An embodiment of the inventive set of the flexible container 2 and the gas pressure vessel 7 is photographically shown in Fig. 2a. It can be seen how the gas pressure vessel 7 is connected via a small (black) hose to the container 2.
  • the opening of the container 2 is closable, wherein the closure mechanism is assigned to the gas pressure vessel 7 in this embodiment or arranged in this.
  • the container 2 still has other connections, which can be seen on the right side of the image and serve, for example, the filling and emptying of the container 2.
  • the exemplary container 2 shown in Fig. 2a is designed as a so-called single-use bag, d. H. it is intended for disposal after a single use.
  • Such containers may have a nominal capacity of, for example, 10 liters.
  • Fig. 2b the container 2 is shown together with the gas pressure vessel 7 in completely surrounded by the gas-permeable layer 3 and surrounded and disposed within the bag 4 state. After closing the bag 4, the arrangement, as shown in Fig. 2b, before. (The detector 8 is not shown in Fig. 2b.) It should be noted that in the evacuated state, of course, usually no distance between the gas-permeable layer 3 and the container 2 and the bag 4 is made. In Figure 2b, these distances are shown only for clarity.
  • the gas pressure container can then deliver a defined amount of helium into the container 2. For this purpose, for example, a special valve can be used.
  • the gas pressure vessel 7 also called “helium applicator” is also intended for single use in the present case, but can of course also be designed for reuse.
  • the relatively small amount of helium avoids overpressure (i.e., far exceeding the normal ambient pressure level of 1 bar) in the container 2.
  • the evacuation can occur before or after the introduction of the helium into the container 2.
  • too long a waiting time between the filling of the container 2 and the detection of the helium by the detector 8 should not elapse, since otherwise a diffusion of the helium through the container 2 can falsify the measurement result.
  • a further advantage of using the gas-permeable layer may be that the volume to be evacuated is substantially less gas-tight bag 4, which increases the ratio of helium (if a leak is present) to the ambient air.
  • Whether or not there is a leak can be output via a user interface at the detector 8, for example.
  • the invention can provide for lower mechanical load of the container to be checked 2, reduces the security risk and the test cost.

Landscapes

  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Examining Or Testing Airtightness (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

L'invention concerne un procédé de contrôle de l'étanchéité d'un récipient flexible (2) pour un fluide, en particulier un médicament fluide. Selon le procédé, le récipient (2) est recouvert au moins partiellement, de préférence complètement, d'une couche perméable aux gaz (3), le récipient (2) avec la couche perméable aux gaz (3) est disposé dans une poche flexible (4) sensiblement étanche aux gaz (4), la poche sensiblement étanche aux gaz (4) est mise sous vide par pompage au moyen d'une ouverture de poche (5), le récipient (2) est rempli d'un gaz rare et la présence de gaz rare, qui sort du récipient (2) par une fuite, à travers la couche perméable aux gaz, par l'ouverture de poche (5), est détectée.
PCT/AT2018/060050 2017-02-24 2018-02-23 Procédé de contrôle de l'étanchéité d'un récipient flexible WO2018152561A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
SG11201903073VA SG11201903073VA (en) 2017-02-24 2018-02-23 Method for inspecting a seal of a flexible container
EP18719739.7A EP3500833B1 (fr) 2017-02-24 2018-02-23 Procédé de contrôle de l'étanchéité d'un récipient flexible
CN201880004508.5A CN109983316B (zh) 2017-02-24 2018-02-23 用于检测柔性容器的密封性的方法和组件在方法中的应用
US16/374,020 US11262268B2 (en) 2017-02-24 2019-04-03 Method for inspecting a seal of a flexible container

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
ATA60014/2017 2017-02-24
AT600142017 2017-02-24
ATA50408/2017A AT519682A1 (de) 2017-02-24 2017-05-12 Verfahren zum Überprüfen einer Dichtheit eines flexiblen Behälters
ATA50408/2017 2017-05-12

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US16/374,020 Continuation US11262268B2 (en) 2017-02-24 2019-04-03 Method for inspecting a seal of a flexible container

Publications (2)

Publication Number Publication Date
WO2018152561A1 true WO2018152561A1 (fr) 2018-08-30
WO2018152561A8 WO2018152561A8 (fr) 2019-05-02

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112284638A (zh) * 2020-10-26 2021-01-29 北京卫星环境工程研究所 一种航天器柔性产品检漏试验辅助装置

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62112027A (ja) * 1985-11-11 1987-05-23 Shinkosumosu Denki Kk 容器の漏洩検知方法
US20120128275A1 (en) * 2009-06-18 2012-05-24 Sartorius Stedim Biotech S.A. Poche a temoin de perte d'integrite incorpore, procede de realisation d'une telle poche et procede d'utilisation
DE102011106165A1 (de) * 2011-06-30 2013-01-03 Sartorius Stedim Biotech Gmbh Prüfverfahren und -vorrichtung für Bioreaktorbehälter sowie Verwendung
US8910509B2 (en) * 2008-03-31 2014-12-16 Pall Technology Uk Limited Apparatus and method for the integrity testing of flexible containers
DE202014010756U1 (de) * 2014-09-12 2016-07-25 Sartorius Stedim Biotech Gmbh Vorrichtung zur Durchführung eines Integritätstests an einem flexiblen Testbehälter

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62112027A (ja) * 1985-11-11 1987-05-23 Shinkosumosu Denki Kk 容器の漏洩検知方法
US8910509B2 (en) * 2008-03-31 2014-12-16 Pall Technology Uk Limited Apparatus and method for the integrity testing of flexible containers
US20120128275A1 (en) * 2009-06-18 2012-05-24 Sartorius Stedim Biotech S.A. Poche a temoin de perte d'integrite incorpore, procede de realisation d'une telle poche et procede d'utilisation
DE102011106165A1 (de) * 2011-06-30 2013-01-03 Sartorius Stedim Biotech Gmbh Prüfverfahren und -vorrichtung für Bioreaktorbehälter sowie Verwendung
DE202014010756U1 (de) * 2014-09-12 2016-07-25 Sartorius Stedim Biotech Gmbh Vorrichtung zur Durchführung eines Integritätstests an einem flexiblen Testbehälter

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112284638A (zh) * 2020-10-26 2021-01-29 北京卫星环境工程研究所 一种航天器柔性产品检漏试验辅助装置

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