METHOD OF INTEGRITY TESTING OF A SINGLE-USE SYSTEM

Abstract

Disclosed is a method of integrity testing of a single-use system for processing a fluidic material. In the inventive method, a single-use system for processing at least one fluidic material is provided. The single-use system has at least one plastic component. A test gas is applied to a lumen of the single-use system. The test gas has one or more of spectral absorption or spectral emission properties in the infrared spectral range distinguishable from ambient air. At least a part of the single-use system is monitored using an infrared camera. A method of processing a fluidic material by using a single-use system and a test system for integrity testing of a single-use system are also disclosed.

Claims

1. A method of integrity testing of a single-use system for processing at least one fluidic material, the method comprising: i.) providing at least one single-use system for processing at least one fluidic material, the single-use system having at least one plastic component; ii.) applying at least one test gas to at least one lumen of the single-use system, wherein the test gas has one or more of spectral absorption or spectral emission properties in the infrared spectral range distinguishable from ambient air; and iii.) monitoring at least a part of the single-use system by using an infrared camera.

2. The method according to claim 1, wherein the test gas comprises carbon dioxide.

3. The method according to claim 1, wherein the method is performed in ambient air, wherein the ambient air has a flow velocity u selected from the group consisting of 0 m/s<u≤0.5 m/s and 0.05 m/s≤u≤0.3 m/s.

4. The method according to claim 1, further comprising using at least one flow controller configured for controlling at least one of a flow velocity of the ambient air, a mass flow rate of the ambient air, and a volume flow rate of the ambient air.

5. The method according to claim 1, wherein the at least one plastic component is selected from the group consisting of: at least one connector element at least partially made of plastic; at least one tubing element at least partially made of plastic; at least one bag element at least partially made of plastic; at least one container element at least partially made of plastic; at least one valve element at least partially made of plastic; at least one filter capsule; at least one sampling system comprising at least one bag and/or at least one capsule; and at least one syringe.

6. The method according to claim 1, wherein step iii.) comprises providing at least one background element, wherein the at least one part of the single-use system monitored by using the infrared camera is positioned at least partially between the background element and the infrared camera.

7. The method according to claim 1, wherein the single-use-system is positioned at a distance d from the infrared camera, wherein 0 m<d≤2 m.

8. The method according to claim 1, wherein the single-use-system is positioned at a distance L from the at least one background element, wherein 0 m≤L≤0.5 m.

9. The method according to claim 6, wherein the background element comprises at least one visually uniform background screen.

10. The method according to claim 6, wherein the background element is mechanically connected to the infrared camera.

11. The method according to claim 6, wherein the background element is temperature-controlled.

12. The method according to claim 6, wherein the background element is at least one of actively heated or actively cooled.

13. The method according to claim 12, wherein the background element is at least one of actively heated or actively cooled by at least one of a fluidic tempering element and an electric tempering element.

14. The method according to claim 13, wherein any one of the fluidic tempering element and/or the electric tempering element is arranged in meanders within the background element.

15. The method according to claim 6, wherein the background element is at least partially made of one or more of a plastic material, a ceramic material, and a metal material.

16. The method according to claim 6, wherein the integrity testing is performed at an ambient temperature and the background element is maintained at a background temperature differing from the ambient temperature, wherein the background temperature differs from the ambient temperature by at least 2 K.

17. The method according to claim 16, wherein the background temperature is higher than the ambient temperature.

18. The method according to claim 16, wherein the ambient temperature is room temperature and wherein the background temperature is 26° C. to 60° C.

19. The method according to claim 1, further comprising returning at least one integrity result that quantifies and/or qualifies the integrity of the single-use system.

20. The method according to claim 1, wherein step iii.) comprises visually detecting the egression of test gas from the single-use system.

21. The method according to claim 20, wherein the visually detecting the egression comprises detecting at least one of a jet, a stream, a cloud or a mist of the test gas, wherein the method comprises automatically quantifying a leakage of the single-use system by visually evaluating the jet, the stream, the cloud or the mist of the test gas, respectively.

22. The method according to claim 1, further comprising using automatic image recognition.

23. The method according to claim 1, wherein, in step ii.), the test gas is applied to the lumen of the single-use system at a pressure of 5 mbar to 300 mbar.

24. The method according to claim 1, wherein step iii.) comprises scanning the single-use system by sequentially monitoring different parts of the single-use system.

25. A method of processing at least one fluidic material using at least one single-use system, the method comprising: I. testing the integrity of the single-use system according to the method of claim 1; and II. connecting the single-use system to at least one supply of at least one fluidic material and at least partially filling the single-use system with the fluidic material.

26. A test system for integrity testing of at least one single-use system for processing at least one fluidic material, the single-use system having at least one plastic component, the test system comprising: a.) at least one test gas supply configured for applying at least one test gas to at least one lumen of the single-use system, wherein the test gas has one or more of spectral absorption or spectral emission properties in the infrared spectral range being distinguishable from ambient air; and b.) at least one infrared camera for monitoring at least a part of the single-use system.

27. The test system according to claim 26, further comprising: c.) at least one evaluation device for evaluating the integrity of the single-use system, wherein the evaluation device is configured for deriving at least one item of integrity information from at least one image provided by the infrared camera.

28. The test system according to claim 26, further comprising: d.) at least one background element, wherein the test system is configured such that at least one part of the single-use system is positionable at least partially between the background element and the infrared camera.

29. A processing system for processing at least one fluidic material, comprising: A. at least one single-use system for processing at least one fluidic material, the single-use system having at least one plastic component; B. at least one test system according to claim 26; and C. at least one supply of the fluidic material; wherein, the single-use system is selectively connectable to the test gas supply of the test system and to the supply of the fluidic material.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0154] The above-mentioned aspects of exemplary embodiments will become more apparent and will be better understood by reference to the following description of the embodiments taken in conjunction with the accompanying drawings, wherein:

[0155] FIG. 1 shows embodiments of a processing system, a test system and a single-use system;

[0156] FIG. 2 shows a flow chart of an embodiment of a method of processing at least one fluidic material by using at least one single-use system and of an embodiment of a method of integrity testing;

[0157] FIG. 3A shows an image of a part of a single-use system, without using a temperature-controlled background element;

[0158] FIG. 3B shows an image of the part of a single-use system of FIG. 3A, using a temperature-controlled background element; and

[0159] FIG. 4 shows an example of an image for leakage testing of a component of a single-use system.

DESCRIPTION

[0160] The embodiments described below are not intended to be exhaustive or to limit the invention to the precise forms disclosed in the following description. Rather, the embodiments are chosen and described so that others skilled in the art may appreciate and understand the principles and practices of this disclosure.

[0161] In FIG. 1, an embodiment of a processing system 110 for processing at least one fluidic material 112 is illustrated. Further, FIG. 1 shows an embodiment of a test system 114 for integrity testing of at least one single-use system 116 for processing the at least one fluidic material 112. The processing system 110 comprises the single-use system 116 for processing the fluidic material 112, and at least one supply 118 of the fluidic material 112. Further, the processing system 110 comprises the test system 114. The processing system 110 may specifically be configured for performing a method 117 of processing at least one fluidic material 112 by using at least one single-use system 116. The method 117 will be described with reference to exemplary embodiments shown in a flowchart illustrated in FIG. 2.

[0162] The test system 114 comprises at least one test gas supply 120, specifically at least one test gas supply 120 connectable to at least one connector 122 of the single-use system 116. The test gas supply 120 is configured for applying at least one test gas 124 to at least one lumen, e.g., to a volume, of the single-use system 116. Specifically, the test gas 124 has one or more of spectral absorption or spectral emission properties in the infrared spectral range being distinguishable from ambient air. Further, the test system 114 comprises at least one infrared camera 126 for monitoring at least a part of the single-use system 116. For example and as outlined above, a commercially available infrared camera may be used, such as a portable infrared camera or a stationary infrared camera, such as available from FLIR Systems, Inc., Wilsonville, Oreg., USA. As an example, a camera of the type GF343 was used in the experiments, e.g., for capturing the images of FIGS. 3A, 3B and 4 discussed in further detail below.

[0163] In the processing system 110, the single-use system may be selectively connectable to the test gas supply 120 of the test system 114 and to the supply 118 of the fluidic material 112, such as in a switchable fashion, for example by way of the connector 122, e.g., by 3-way valve.

[0164] Further, the test system 114 may comprise at least one evaluation device 128 for evaluating the integrity of the single-use system 116. In particular, the evaluation device 128 may be configured for deriving at least one item of integrity information from at least one image provided by the infrared camera 126. Thus, the evaluation device 128 and the infrared camera 126 may be configured for transmitting information, such as for transmitting the at least one image and/or at least one setting information, as is exemplarily illustrated in FIG. 1 by an arrow pointing from the evaluation device 128 to the infrared camera 126 and vice versa. Further, the evaluation device 128 may be used for controlling the connector 122, e.g., the 3-way valve, as is exemplarily illustrated in FIG. 1 by an arrow pointing from the evaluation device 128 to the connector 122 and vice versa. The evaluation device 128 further may comprise at least one processor 130.

[0165] The test system 114 may further comprise at least one background element 132. The background element 132 specifically may be temperature controlled, e.g., by using at least one temperature sensor 133 and/or at least one temperature controller. As an example, the background element 132 may be temperature controlled by using at least one heating and/or at least one cooling element and/or by using at least one temperature controller. Thus, as an example, the background element 132 may be kept at a temperature different from the ambient temperature and/or the temperature of the single-use system 116. As an example, as outlined above, a temperature difference between the background element and the ambient temperature and/or the temperature of the single-use system 116 of 2-10 K may be maintained, such as a temperature difference of 3-5 K.

[0166] Specifically, the test system 114 may be configured such that at least one part of the single-use system 116 may be positionable at least partially between the background element 132 and the infrared camera 126. The background element 132 and/or the camera 126 may be connected, e.g., by at least one connecting element 135, or may also be positionable independently. In particular, mechanically connecting the infrared camera 126 and the background element 132 by way of the connecting element 135, as illustrated in FIG. 1, may be an optional feature. The background element 132 and/or the camera 126 may also be positionable by one or more stages, e.g., automated stages, such as for automated testing, as indicated by the arrows at elements 126 and 132 in FIG. 1.

[0167] The test system 114 may specifically be configured for performing a method 134 of integrity testing of a single-use system 116 for processing at least one fluidic material 112. The method 134 will be described with reference to exemplary embodiments shown in a flowchart illustrated in FIG. 2.

[0168] The method 134 of integrity testing of a single-use system 116 for processing at least one fluidic material 112 comprises the following steps, which may specifically be performed in the given order. Still, a different order may also be possible. It may be possible to perform two or more of the method steps fully or partially simultaneously. It may further be possible to perform one, more than one or even all of the method steps once or repeatedly. The method 134 may comprise additional method steps that are not listed. The method steps are the following: [0169] i.) (denoted with reference number 136) providing at least one single-use system 116 for processing at least one fluidic material 112, the single-use system 116 having at least one plastic component; [0170] ii.) (denoted with reference number 138) applying, specifically via at least one connector 122 of the single-use system 116, at least one test gas 124 to at least one lumen of the single-use system 116, wherein the test gas 124 has one or more of spectral absorption or spectral emission properties in the infrared spectral range being distinguishable from ambient air; and [0171] iii.) (denoted with reference number 140) monitoring at least a part of the single-use system 116 by using an infrared camera 126.

[0172] The application of the one or more test gases in step 138 may, as an example, take place at a low pressure of 20-100 mbar, such as 50 mbar.

[0173] The method 134 may be fully or partially computer-controlled. Specifically, one or more of steps ii.) 138 and iii.) 140 of the method 134 may be computer-controlled.

[0174] The background element 132, as exemplarily illustrated in FIG. 1, may specifically comprise at least one visually uniform background screen 142. Further, the background element 132 may be temperature-controlled. Specifically, as exemplarily illustrated in FIG. 1 by an arrow pointing from the evaluation device 128 to the background element 132 and vice versa, the temperature of the background element 132 may be controlled by using the evaluation device 128. As an example, the background element may be one or both of actively heated or actively cooled. It shall be noted, however, that a passive heating and/or a passive cooling may also be possible.

[0175] Step iii.) 140 may further comprise detecting one or more leakages 144 in the single-use system 116. As an example, the leakage detecting in step iii.) may comprise detecting the egression of test gas 124 from the single-use system 116, wherein specifically at least one jet 146, at least one stream, at least one cloud or at least one mist of the test gas 124 may be detected.

[0176] The method 134 may comprise a further step of returning at least one integrity result (denoted with reference number 148). The integrity result may specifically quantify or qualify the integrity of the single-use system. For returning the at least one integrity result, as an example, the method may further comprise automatically quantifying the leakage 144 of the single-use system, e.g., by visually evaluating the jet 146 of the test gas 124. In particular, image recognition may be used for evaluating a jet profile of the test gas 124.

[0177] In step ii.) 138, the test gas 124 may be applied to the lumen, e.g., to the volume, of the single-use system 116 at a pressure, specifically an overpressure. The pressure of the test gas 124 in the single-use system 116 may be a parameter that should be controlled, defined or at least known in a precise fashion. Thus, the test system 114 may comprise one or more of a pressure regulator 150, a valve 152, a mass-flow meter 154, a pressure meter 156, a clamp 158, a sterile filter or any further element suited for controlling and/or monitoring the pressure or flow of the test gas 124. In particular, information on the pressure and/or on the flow of test gas 124 may be transmitted and processed by using the evaluation device 128, as is exemplarily illustrated in FIG. 1 by arrows pointing from the evaluation device 128 to any one of the pressure regulator 150, the valve 152, the mass-flow meter 154 and the pressure meter 156 and vice versa.

[0178] The method 134 of integrity testing of a single-use system 116 may be comprised by the method 117 of processing at least one fluidic material 112 by using at least one single-use system 116. In particular, the method 117 of processing at least one fluidic material 112 by using at least one single-use system 116 comprises the following steps, which may specifically be performed in the given order. Still, a different order may also be possible. It may be possible to perform two or more of the method steps fully or partially simultaneously. It may further be possible to perform one, more than one or even all of the method steps once or repeatedly. The method 117 may comprise additional method steps that are not listed. The method steps are the following: [0179] I. (denoted with reference number 160) testing the integrity of the single-use system 116 by using the method 134 of integrity testing of a single-use system 116; and [0180] II. (denoted with reference number 162) connecting the single-use system 116 to at least one supply 118 of at least one fluidic material 112 and at least partially filling the single-use system 116 with the fluidic material 112.

[0181] Further, as exemplarily illustrated in FIG. 2, the method 117 may comprise a branching point 164. The branching point 164 may indicate a condition query, such as deciding between a first branch 166 and a second branch 168. For example, the condition query may make use of the integrity result. Specifically, the integrity result may comprise at least one item of information quantifying and/or qualifying the integrity of the single-use system 116. As an example, the first branch 166 may indicate integrity of the single-use system 116, such as indicating the single-use system 116 to be sufficiently intact. Thus, the first branch 166 leads to step II. 162, wherein the single-use system 116 may be connected to the supply 118 of the fluidic material 112 and subsequently be filled with the fluidic material 112.

[0182] The second branch 168 may indicate the single-use system 116 to not be sufficiently intact, e.g., to comprise at least one leakage such that the single-use system 116 does not fulfill an integrity criteria necessary to be fulfilled in order for the single-use system 116 to be used in the method 117 of processing at least one fluidic material 112 by using at least one single-use system 116. Thus, the second branch 168 leads to aborting the method 117, the step of aborting being denoted with reference number 170.

[0183] In FIGS. 3A, 3B and 4, examples of images captured by using the method of FIG. 2 are shown. The images were taken by using the above-mentioned infrared camera GF343 by FLIR Systems, Inc.

[0184] Thus, firstly, in FIGS. 3A and 3B, the significant improvements of image recognition by using the background element 132 are demonstrated. Both images were taken at room temperature of 22° C. In FIG. 3A, an image of a part of a single-use system is shown without using any background element. It is clearly visible that the contrast of the image is rather low. Specifically, neither tubing walls nor details of the surfaces of the elements are visible. Contrarily, in FIG. 3B, an image of the same setup captured with a background element is shown, wherein the background element was kept at a temperature different from the room temperature. In this case, a fluid-heated background element, having a temperature of 28° C., was used. It is clearly visible that the contrast was greatly improved by this measure. Thus, the walls of the tubings are clearly visible, and fine details of the structures can be detected.

[0185] In FIG. 4, an image of a leakage test is shown, using the heated background element as in FIG. 3B. Therein, a plastic tube was perforated with a cannula having a diameter of 50 μm. The plastic tube was pressurized with carbon dioxide having a pressure of 50 mbar. The five leakages intentionally inserted into the tubing wall for this purpose are clearly visible by detecting gas jets of the test gas in the image. Image analysis, such as automated image recognition software, may be used for analyzing the gas jets. Thereby, with the knowledge of the pressure and data derived from the image analysis, the location and even the size of the leakages may be derived.

[0186] While exemplary embodiments have been disclosed hereinabove, the present invention is not limited to the disclosed embodiments. Instead, this application is intended to cover any variations, uses, or adaptations of this disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims.

LIST OF REFERENCE NUMBERS

[0187] 110 processing system [0188] 112 fluidic material [0189] 114 test system [0190] 116 single-use system [0191] 117 method of processing at least one fluidic material [0192] 118 supply of fluidic material [0193] 120 test gas supply [0194] 122 connector [0195] 124 test gas [0196] 126 infrared camera [0197] 128 evaluation device [0198] 130 processor [0199] 132 background element [0200] 133 temperature sensor [0201] 134 method of integrity testing of a single-use system [0202] 135 connecting element [0203] 136 step i.) [0204] 138 step ii.) [0205] 140 step iii.) [0206] 142 background screen [0207] 144 leakage [0208] 146 jet of test gas [0209] 148 returning at least one integrity result [0210] 150 pressure regulator [0211] 152 valve [0212] 154 mass-flow meter [0213] 156 pressure meter [0214] 158 clamp [0215] 160 step I. [0216] 162 step II. [0217] 164 branching point [0218] 166 first branch [0219] 168 second branch [0220] 170 aborting the method